To see the other types of publications on this topic, follow the link: Mitochondria. DNA.
Journal articles on the topic 'Mitochondria. DNA'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Mitochondria. DNA.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Basu, Urmimala, Alicia M. Bostwick, Kalyan Das, Kristin E. Dittenhafer-Reed, and Smita S. Patel. "Structure, mechanism, and regulation of mitochondrial DNA transcription initiation." Journal of Biological Chemistry 295, no. 52 (October 30, 2020): 18406–25. http://dx.doi.org/10.1074/jbc.rev120.011202.
Full textAbstract:
Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.
2
Varma, V. A., C. M. Cerjan, K. L. Abbott, and S. B. Hunter. "Non-isotopic in situ hybridization method for mitochondria in oncocytes." Journal of Histochemistry & Cytochemistry 42, no. 2 (February 1994): 273–76. http://dx.doi.org/10.1177/42.2.8288868.
Full textAbstract:
We used in situ hybridization to specifically identify mitochondria in a series of formalin-fixed, paraffin-embedded oncocytic lesions. Digoxigenin-labeled DNA probes were generated by the polymerase chain reaction (PCR), with primers designed to amplify a mitochondrion-specific 154 BP sequence within the ND4 coding region. Probes were hybridized with mitochondrial DNA under stringent conditions. Oncocytes were strongly and consistently stained, reflecting the high copy number of mitochondrial DNA within these cells. Because of the presence of endogenous biotin within mitochondria, digoxigenin is preferable to biotin as a label for detection of mitochondria.
3
Valdés-Aguayo, José J., Idalia Garza-Veloz, José I. Badillo-Almaráz, Sofia Bernal-Silva, Maria C. Martínez-Vázquez, Vladimir Juárez-Alcalá, José R. Vargas-Rodríguez, et al. "Mitochondria and Mitochondrial DNA: Key Elements in the Pathogenesis and Exacerbation of the Inflammatory State Caused by COVID-19." Medicina 57, no. 9 (September 3, 2021): 928. http://dx.doi.org/10.3390/medicina57090928.
Full textAbstract:
Background and Objectives. The importance of mitochondria in inflammatory pathologies, besides providing energy, is associated with the release of mitochondrial damage products, such as mitochondrial DNA (mt-DNA), which may perpetuate inflammation. In this review, we aimed to show the importance of mitochondria, as organelles that produce energy and intervene in multiple pathologies, focusing mainly in COVID-19 and using multiple molecular mechanisms that allow for the replication and maintenance of the viral genome, leading to the exacerbation and spread of the inflammatory response. The evidence suggests that mitochondria are implicated in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which forms double-membrane vesicles and evades detection by the cell defense system. These mitochondrion-hijacking vesicles damage the integrity of the mitochondrion’s membrane, releasing mt-DNA into circulation and triggering the activation of innate immunity, which may contribute to an exacerbation of the pro-inflammatory state. Conclusions. While mitochondrial dysfunction in COVID-19 continues to be studied, the use of mt-DNA as an indicator of prognosis and severity is a potential area yet to be explored.
4
Baysal, Bora. "Mitochondria: More than Mitochondrial DNA in Cancer." PLoS Medicine 3, no. 3 (March 28, 2006): e156. http://dx.doi.org/10.1371/journal.pmed.0030156.
Full text
5
Faria, Rúben, Eric Vivés, Prisca Boisguerin, Angela Sousa, and Diana Costa. "Development of Peptide-Based Nanoparticles for Mitochondrial Plasmid DNA Delivery." Polymers 13, no. 11 (June 1, 2021): 1836. http://dx.doi.org/10.3390/polym13111836.
Full textAbstract:
A mitochondrion is a cellular organelle able to produce cellular energy in the form of adenosine triphosphate (ATP). As in the nucleus, mitochondria contain their own genome: the mitochondrial DNA (mtDNA). This genome is particularly susceptible to mutations that are at the basis of a multitude of disorders, especially those affecting the heart, the central nervous system and muscles. Conventional clinical practice applied to mitochondrial diseases is very limited and ineffective; a clear need for innovative therapies is demonstrated. Gene therapy seems to be a promising approach. The use of mitochondrial DNA as a therapeutic, optimized by peptide-based complexes with mitochondrial targeting, can be seen as a powerful tool in the reestablishment of normal mitochondrial function. In line with this requirement, in this work and for the first time, a mitochondrial-targeting sequence (MTS) has been incorporated into previously researched peptides, to confer on them a targeting ability. These peptides were then considered to complex a plasmid DNA (pDNA) which contains the mitochondrial gene ND1 (mitochondrially encoded NADH dehydrogenase 1 protein), aiming at the formation of peptide-based nanoparticles. Currently, the ND1 plasmid is one of the most advanced bioengineered vectors for conducting research on mitochondrial gene expression. The formed complexes were characterized in terms of pDNA complexation capacity, morphology, size, surface charge and cytotoxic profile. These data revealed that the developed carriers possess suitable properties for pDNA delivery. Furthermore, in vitro studies illustrated the mitochondrial targeting ability of the novel peptide/pDNA complexes. A comparison between the different complexes revealed the most promising ones that complex pDNA and target mitochondria. This may contribute to the optimization of peptide-based non-viral systems to target mitochondria, instigating progress in mitochondrial gene therapy.
6
Bertrand, Helmut. "Senescence is coupled to induction of an oxidative phosphorylation stress response by mitochondrial DNA mutations in Neurospora." Canadian Journal of Botany 73, S1 (December 31, 1995): 198–204. http://dx.doi.org/10.1139/b95-246.
Full textAbstract:
In Neurospora and other genera of filamentous fungi, the occurrence of a mutation affecting one or several genes on the chromosome of a single mitochondrion can trigger the gradual displacement of wild-type mitochondrial DNA by mutant molecules in asexually propagated cultures. As this displacement progresses, the cultures senesce gradually and die if the mitochondrial mutation is lethal, or develop respiratory deficiencies if the mutation is nonlethal. Mitochondrial mutations that elicit the displacement of wild-type mitochondrial DNAs are said to be "suppressive." In the strictly aerobic fungi, suppressiveness appears to be associated exclusively with mutations that diminish cytochrome-mediated mitochondrial redox functions and, thus, curtail oxidative phosphorylation. In Neurospora, suppressiveness is connected to a regulatory system through which cells respond to chemical or genetic insults to the mitochondrial electron-transport system by increasing the number of mitochondria approximately threefold. Mutant alleles of two nuclear genes, osr-1 and osr-2, affect this stress response and abrogate the suppressiveness of mitochondrial mutations. Therefore, we propose that mitochondrial mutations are suppressive because their phenotypic effect is limited to the organelles within which the mutant DNA is located. Consequently, mitochondria that are "homozygous" for a mutant allele are functionally crippled and are induced to proliferate more rapidly than the normal mitochondria with which they coexist in a common protoplasm. While this model provides a plausible explanation for the suppressiveness of mitochondrial mutations in the strictly aerobic fungi, it may not account for the biased transmission of mutant mitochondrial DNAs in the facultatively anaerobic yeasts. Key words: mitochondria, mitochondrial DNA, mutations, suppressiveness, oxidative phosphorylation, stress response.
7
Schapira, Anthony. "Mitochondrial DNA and disease: What happens when things go wrong." Biochemist 27, no. 3 (June 1, 2005): 24–27. http://dx.doi.org/10.1042/bio02703024.
Full textAbstract:
Mitochondria are ubiquitous in eukaryotic cells and one of their important functions is to provide ATP via oxidative phosphorylation (OXPHOS). The mitochondria also host other biochemical pathways, including -oxidation, Krebs' citric acid cycle and parts of the urea cycle. Thus, the mitochondria play a pivotal role in cellular biochemistry. The relationship of mitochondria to human disease has been identified only recently, but has now become one of the most rapidly expanding areas of human pathology. Mitochondrial disorders may be a consequence of inherited defects of either the nuclear or mitochondrial genomes or, alternatively, may be due to endogenous or exogenous environmental toxins. This article will focus upon abnormalities of mitochondrial DNA (mtDNA) and human disease.
8
Almannai, Mohammed, Ayman W. El-Hattab, and Fernando Scaglia. "Mitochondrial DNA replication: clinical syndromes." Essays in Biochemistry 62, no. 3 (June 27, 2018): 297–308. http://dx.doi.org/10.1042/ebc20170101.
Full textAbstract:
Each nucleated cell contains several hundreds of mitochondria, which are unique organelles in being under dual genome control. The mitochondria contain their own DNA, the mtDNA, but most of mitochondrial proteins are encoded by nuclear genes, including all the proteins required for replication, transcription, and repair of mtDNA. MtDNA replication is a continuous process that requires coordinated action of several enzymes that are part of the mtDNA replisome. It also requires constant supply of deoxyribonucleotide triphosphates(dNTPs) and interaction with other mitochondria for mixing and unifying the mitochondrial compartment. MtDNA maintenance defects are a growing list of disorders caused by defects in nuclear genes involved in different aspects of mtDNA replication. As a result of defects in these genes, mtDNA depletion and/or multiple mtDNA deletions develop in affected tissues resulting in variable manifestations that range from adult-onset mild disease to lethal presentation early in life.
9
Bradshaw, Patrick C., and David C. Samuels. "A computational model of mitochondrial deoxynucleotide metabolism and DNA replication." American Journal of Physiology-Cell Physiology 288, no. 5 (May 2005): C989—C1002. http://dx.doi.org/10.1152/ajpcell.00530.2004.
Full textAbstract:
We present a computational model of mitochondrial deoxynucleotide metabolism and mitochondrial DNA (mtDNA) synthesis. The model includes the transport of deoxynucleosides and deoxynucleotides into the mitochondrial matrix space, as well as their phosphorylation and polymerization into mtDNA. Different simulated cell types (cancer, rapidly dividing, slowly dividing, and postmitotic cells) are represented in this model by different cytoplasmic deoxynucleotide concentrations. We calculated the changes in deoxynucleotide concentrations within the mitochondrion during the course of a mtDNA replication event and the time required for mtDNA replication in the different cell types. On the basis of the model, we define three steady states of mitochondrial deoxynucleotide metabolism: the phosphorylating state (the net import of deoxynucleosides and export of phosphorylated deoxynucleotides), the desphosphorylating state (the reverse of the phosphorylating state), and the efficient state (the net import of both deoxynucleosides and deoxynucleotides). We present five testable hypotheses based on this simulation. First, the deoxynucleotide pools within a mitochondrion are sufficient to support only a small fraction of even a single mtDNA replication event. Second, the mtDNA replication time in postmitotic cells is much longer than that in rapidly dividing cells. Third, mitochondria in dividing cells are net sinks of cytoplasmic deoxynucleotides, while mitochondria in postmitotic cells are net sources. Fourth, the deoxynucleotide carrier exerts the most control over the mtDNA replication rate in rapidly dividing cells, but in postmitotic cells, the NDPK and TK2 enzymes have the most control. Fifth, following from the previous hypothesis, rapidly dividing cells derive almost all of their mtDNA precursors from the cytoplasmic deoxynucleotides, not from phosphorylation within the mitochondrion.
10
Wang, Sheng-Fan, Shiuan Chen, Ling-Ming Tseng, and Hsin-Chen Lee. "Role of the mitochondrial stress response in human cancer progression." Experimental Biology and Medicine 245, no. 10 (April 23, 2020): 861–78. http://dx.doi.org/10.1177/1535370220920558.
Full textAbstract:
Mitochondria are important organelles that are responsible for cellular energy metabolism, cellular redox/calcium homeostasis, and cell death regulation in mammalian cells. Mitochondrial dysfunction is involved in various diseases, such as neurodegenerative diseases, cardiovascular diseases, immune disorders, and cancer. Defective mitochondria and metabolism remodeling are common characteristics in cancer cells. Several factors, such as mitochondrial DNA copy number changes, mitochondrial DNA mutations, mitochondrial enzyme defects, and mitochondrial dynamic changes, may contribute to mitochondrial dysfunction in cancer cells. Some lines of evidence have shown that mitochondrial dysfunction may promote cancer progression. Here, several mitochondrial stress responses, including the mitochondrial unfolded protein response and the integrated stress response, and several mitochondrion-derived molecules (reactive oxygen species, calcium, oncometabolites, and others) are reviewed; these pathways and molecules are considered to act as retrograde signaling regulators in the development and progression of cancer. Targeting these components of the mitochondrial stress response may be an important strategy for cancer treatment. Impact statement Dysregulated mitochondria often occurred in cancers. Mitochondrial dysfunction might contribute to cancer progression. We reviewed several mitochondrial stresses in cancers. Mitochondrial stress responses might contribute to cancer progression. Several mitochondrion-derived molecules (ROS, Ca2+, oncometabolites, exported mtDNA, mitochondrial double-stranded RNA, humanin, and MOTS-c), integrated stress response, and mitochondrial unfolded protein response act as retrograde signaling pathways and might be critical in the development and progression of cancer. Targeting these mitochondrial stress responses may be an important strategy for cancer treatment.
11
Campbell, C. L., and P. E. Thorsness. "Escape of mitochondrial DNA to the nucleus in yme1 yeast is mediated by vacuolar-dependent turnover of abnormal mitochondrial compartments." Journal of Cell Science 111, no. 16 (August 15, 1998): 2455–64. http://dx.doi.org/10.1242/jcs.111.16.2455.
Full textAbstract:
Inactivation of Yme1p, a mitochondrially-localized ATP-dependent metallo-protease in the yeast Saccharomyces cerevisiae, causes a high rate of DNA escape from mitochondria to the nucleus as well as pleiotropic functional and morphological mitochondrial defects. The evidence presented here suggests that the abnormal mitochondria of a yme1 strain are degraded by the vacuole. First, electron microscopy of Yme1p-deficient strains revealed mitochondria physically associated with the vacuole via electron dense structures. Second, disruption of vacuolar function affected the frequency of mitochondrial DNA escape from yme1 and wild-type strains. Both PEP4 or PRC1 gene disruptions resulted in a lower frequency of mitochondrial DNA escape. Third, an in vivo assay that monitors vacuole-dependent turnover of the mitochondrial compartment demonstrated an increased rate of mitochondrial turnover in yme1 yeast when compared to the rate found in wild-type yeast. In this assay, vacuolar alkaline phosphatase, encoded by PHO8, was targeted to mitochondria in a strain bearing disruption to the genomic PHO8 locus. Maturation of the mitochondrially localized alkaline phosphatase pro-enzyme requires proteinase A, which is localized in the vacuole. Therefore, alkaline phosphatase activity reflects vacuole-dependent turnover of mitochondria. This assay reveals that mitochondria of a yme1 strain are taken up by the vacuole more frequently than mitochondria of an isogenic wild-type strain when these yeast are cultured in medium necessitating respiratory growth. Degradation of abnormal mitochondria is one pathway by which mitochondrial DNA escapes and migrates to the nucleus.
12
Wang, Jie, Fei Lin, Li-li Guo, Xing-jiang Xiong, and Xun Fan. "Cardiovascular Disease, Mitochondria, and Traditional Chinese Medicine." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/143145.
Full textAbstract:
Recent studies demonstrated that mitochondria play an important role in the cardiovascular system and mutations of mitochondrial DNA affect coronary artery disease, resulting in hypertension, atherosclerosis, and cardiomyopathy. Traditional Chinese medicine (TCM) has been used for thousands of years to treat cardiovascular disease, but it is not yet clear how TCM affects mitochondrial function. By reviewing the interactions between the cardiovascular system, mitochondrial DNA, and TCM, we show that cardiovascular disease is negatively affected by mutations in mitochondrial DNA and that TCM can be used to treat cardiovascular disease by regulating the structure and function of mitochondria via increases in mitochondrial electron transport and oxidative phosphorylation, modulation of mitochondrial-mediated apoptosis, and decreases in mitochondrial ROS. However further research is still required to identify the mechanism by which TCM affects CVD and modifies mitochondrial DNA.
13
Mustafa, Mohd Fazirul, Sharida Fakurazi, Maizaton Atmadini Abdullah, and Sandra Maniam. "Pathogenic Mitochondria DNA Mutations: Current Detection Tools and Interventions." Genes 11, no. 2 (February 12, 2020): 192. http://dx.doi.org/10.3390/genes11020192.
Full textAbstract:
Mitochondria are best known for their role in energy production, and they are the only mammalian organelles that contain their own genomes. The mitochondrial genome mutation rate is reported to be 10–17 times higher compared to nuclear genomes as a result of oxidative damage caused by reactive oxygen species during oxidative phosphorylation. Pathogenic mitochondrial DNA mutations result in mitochondrial DNA disorders, which are among the most common inherited human diseases. Interventions of mitochondrial DNA disorders involve either the transfer of viable isolated mitochondria to recipient cells or genetically modifying the mitochondrial genome to improve therapeutic outcome. This review outlines the common mitochondrial DNA disorders and the key advances in the past decade necessary to improve the current knowledge on mitochondrial disease intervention. Although it is now 31 years since the first description of patients with pathogenic mitochondrial DNA was reported, the treatment for mitochondrial disease is often inadequate and mostly palliative. Advancements in diagnostic technology improved the molecular diagnosis of previously unresolved cases, and they provide new insight into the pathogenesis and genetic changes in mitochondrial DNA diseases.
14
Ghosh, Arijit, Sangheeta Bhattacharjee, Srijita Paul Chowdhuri, Abhik Mallick, Ishita Rehman, Sudipta Basu, and Benu Brata Das. "SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy." Science Advances 5, no. 11 (November 2019): eaax9778. http://dx.doi.org/10.1126/sciadv.aax9778.
Full textAbstract:
A homozygous mutation of human tyrosyl-DNA phosphodiesterase 1 (TDP1) causes the neurodegenerative syndrome, spinocerebellar ataxia with axonal neuropathy (SCAN1). TDP1 hydrolyzes the phosphodiester bond between DNA 3′-end and a tyrosyl moiety within trapped topoisomerase I (Top1)-DNA covalent complexes (Top1cc). TDP1 is critical for mitochondrial DNA (mtDNA) repair; however, the role of mitochondria remains largely unknown for the etiology of SCAN1. We demonstrate that mitochondria in cells expressing SCAN1-TDP1 (TDP1H493R) are selectively trapped on mtDNA in the regulatory non-coding region and promoter sequences. Trapped TDP1H493R-mtDNA complexes were markedly increased in the presence of the Top1 poison (mito-SN38) when targeted selectively into mitochondria in nanoparticles. TDP1H493R-trapping accumulates mtDNA damage and triggers Drp1-mediated mitochondrial fission, which blocks mitobiogenesis. TDP1H493R prompts PTEN-induced kinase 1–dependent mitophagy to eliminate dysfunctional mitochondria. SCAN1-TDP1 in mitochondria creates a pathological state that allows neurons to turn on mitophagy to rescue fit mitochondria as a mechanism of survival.
15
Cavalcante, Giovanna C., Leandro Magalhães, Ândrea Ribeiro-dos-Santos, and Amanda F. Vidal. "Mitochondrial Epigenetics: Non-Coding RNAs as a Novel Layer of Complexity." International Journal of Molecular Sciences 21, no. 5 (March 6, 2020): 1838. http://dx.doi.org/10.3390/ijms21051838.
Full textAbstract:
Mitochondria are organelles responsible for several functions involved in cellular balance, including energy generation and apoptosis. For decades now, it has been well-known that mitochondria have their own genetic material (mitochondrial DNA), which is different from nuclear DNA in many ways. More recently, studies indicated that, much like nuclear DNA, mitochondrial DNA is regulated by epigenetic factors, particularly DNA methylation and non-coding RNAs (ncRNAs). This field is now called mitoepigenetics. Additionally, it has also been established that nucleus and mitochondria are constantly communicating to each other to regulate different cellular pathways. However, little is known about the mechanisms underlying mitoepigenetics and nuclei–mitochondria communication, and also about the involvement of the ncRNAs in mitochondrial functions and related diseases. In this context, this review presents the state-of-the-art knowledge, focusing on ncRNAs as new players in mitoepigenetic regulation and discussing future perspectives of these fields.
16
Nakayama, Hiroyuki, and Kinya Otsu. "Mitochondrial DNA as an inflammatory mediator in cardiovascular diseases." Biochemical Journal 475, no. 5 (March 6, 2018): 839–52. http://dx.doi.org/10.1042/bcj20170714.
Full textAbstract:
Mitochondria play a central role in multiple cellular functions, including energy production, calcium homeostasis, and cell death. Currently, growing evidence indicates the vital roles of mitochondria in triggering and maintaining inflammation. Chronic inflammation without microbial infection — termed sterile inflammation — is strongly involved in the development of heart failure. Sterile inflammation is triggered by the activation of pattern recognition receptors (PRRs) that sense endogenous ligands called damage-associated molecular patterns (DAMPs). Mitochondria release multiple DAMPs including mitochondrial DNA, peptides, and lipids, which induce inflammation via the stimulation of multiple PRRs. Among the mitochondrial DAMPs, mitochondrial DNA (mtDNA) is currently highlighted as the DAMP that mediates the activation of multiple PRRs, including Toll-like receptor 9, Nod-like receptors, and cyclic GMP–AMP synthetase/stimulator of interferon gene pathways. These PRR signalling pathways, in turn, lead to the activation of nuclear factor-κB and interferon regulatory factor, which enhances the transcriptional activity of inflammatory cytokines and interferons, and induces the recruitment of inflammatory cells. As the heart is an organ comprising abundant mitochondria for its ATP consumption (needed to maintain constant cyclic contraction and relaxation), the generation of massive amounts of mitochondrial radical oxygen species and mitochondrial DAMPs are predicted to occur and promote cardiac inflammation. Here, we will focus on the role of mtDNA in cardiac inflammation and review the mechanism and pathological significance of mtDNA-induced inflammatory responses in cardiac diseases.
17
Dahal, Sumedha, and Sathees C. Raghavan. "Mitochondrial genome stability in human: understanding the role of DNA repair pathways." Biochemical Journal 478, no. 6 (March 19, 2021): 1179–97. http://dx.doi.org/10.1042/bcj20200920.
Full textAbstract:
Mitochondria are semiautonomous organelles in eukaryotic cells and possess their own genome that replicates independently. Mitochondria play a major role in oxidative phosphorylation due to which its genome is frequently exposed to oxidative stress. Factors including ionizing radiation, radiomimetic drugs and replication fork stalling can also result in different types of mutations in mitochondrial DNA (mtDNA) leading to genome fragility. Mitochondria from myopathies, dystonia, cancer patient samples show frequent mtDNA mutations such as point mutations, insertions and large-scale deletions that could account for mitochondria-associated disease pathogenesis. The mechanism by which such mutations arise following exposure to various DNA-damaging agents is not well understood. One of the well-studied repair pathways in mitochondria is base excision repair. Other repair pathways such as mismatch repair, homologous recombination and microhomology-mediated end joining have also been reported. Interestingly, nucleotide excision repair and classical nonhomologous DNA end joining are not detected in mitochondria. In this review, we summarize the potential causes of mitochondrial genome fragility, their implications as well as various DNA repair pathways that operate in mitochondria.
18
Nomura, Yasutomo. "Direct Quantification of Mitochondria and Mitochondrial DNA Dynamics." Current Pharmaceutical Biotechnology 13, no. 14 (December 18, 2012): 2617–22. http://dx.doi.org/10.2174/138920101314151120122752.
Full text
19
Reiner, Joseph E., Rani B. Kishore, Barbara C. Levin, Thomas Albanetti, Nicholas Boire, Ashley Knipe, Kristian Helmerson, and Koren Holland Deckman. "Detection of Heteroplasmic Mitochondrial DNA in Single Mitochondria." PLoS ONE 5, no. 12 (December 16, 2010): e14359. http://dx.doi.org/10.1371/journal.pone.0014359.
Full text
20
Peter, Bradley, and Maria Falkenberg. "TWINKLE and Other Human Mitochondrial DNA Helicases: Structure, Function and Disease." Genes 11, no. 4 (April 9, 2020): 408. http://dx.doi.org/10.3390/genes11040408.
Full textAbstract:
Mammalian mitochondria contain a circular genome (mtDNA) which encodes subunits of the oxidative phosphorylation machinery. The replication and maintenance of mtDNA is carried out by a set of nuclear-encoded factors—of which, helicases form an important group. The TWINKLE helicase is the main helicase in mitochondria and is the only helicase required for mtDNA replication. Mutations in TWINKLE cause a number of human disorders associated with mitochondrial dysfunction, neurodegeneration and premature ageing. In addition, a number of other helicases with a putative role in mitochondria have been identified. In this review, we discuss our current knowledge of TWINKLE structure and function and its role in diseases of mtDNA maintenance. We also briefly discuss other potential mitochondrial helicases and postulate on their role(s) in mitochondria.
21
Ahmad, Niaz, and Brent L. Nielsen. "Plant Organelle DNA Maintenance." Plants 9, no. 6 (May 28, 2020): 683. http://dx.doi.org/10.3390/plants9060683.
Full textAbstract:
Plant cells contain two double membrane bound organelles, plastids and mitochondria, that contain their own genomes. There is a very large variation in the sizes of mitochondrial genomes in higher plants, while the plastid genome remains relatively uniform across different species. One of the curious features of the organelle DNA is that it exists in a high copy number per mitochondria or chloroplast, which varies greatly in different tissues during plant development. The variations in copy number, morphology and genomic content reflect the diversity in organelle functions. The link between the metabolic needs of a cell and the capacity of mitochondria and chloroplasts to fulfill this demand is thought to act as a selective force on the number of organelles and genome copies per organelle. However, it is not yet clear how the activities of mitochondria and chloroplasts are coordinated in response to cellular and environmental cues. The relationship between genome copy number variation and the mechanism(s) by which the genomes are maintained through different developmental stages are yet to be fully understood. This Special Issue has several contributions that address current knowledge of higher plant organelle DNA. Here we briefly introduce these articles that discuss the importance of different aspects of the organelle genome in higher plants.
22
Menger, Katja E., Alejandro Rodríguez-Luis, James Chapman, and Thomas J. Nicholls. "Controlling the topology of mammalian mitochondrial DNA." Open Biology 11, no. 9 (September 2021): 210168. http://dx.doi.org/10.1098/rsob.210168.
Full textAbstract:
The genome of mitochondria, called mtDNA, is a small circular DNA molecule present at thousands of copies per human cell. MtDNA is packaged into nucleoprotein complexes called nucleoids, and the density of mtDNA packaging affects mitochondrial gene expression. Genetic processes such as transcription, DNA replication and DNA packaging alter DNA topology, and these topological problems are solved by a family of enzymes called topoisomerases. Within mitochondria, topoisomerases are involved firstly in the regulation of mtDNA supercoiling and secondly in disentangling interlinked mtDNA molecules following mtDNA replication. The loss of mitochondrial topoisomerase activity leads to defects in mitochondrial function, and variants in the dual-localized type IA topoisomerase TOP3A have also been reported to cause human mitochondrial disease. We review the current knowledge on processes that alter mtDNA topology, how mtDNA topology is modulated by the action of topoisomerases, and the consequences of altered mtDNA topology for mitochondrial function and human health.
23
Knorre, Dmitry A., Konstantin Y. Popadin, Svyatoslav S. Sokolov, and Fedor F. Severin. "Roles of Mitochondrial Dynamics under Stressful and Normal Conditions in Yeast Cells." Oxidative Medicine and Cellular Longevity 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/139491.
Full textAbstract:
Eukaryotic cells contain dynamic mitochondrial filaments: they fuse and divide. Here we summarize data on the protein machinery driving mitochondrial dynamics in yeast and also discuss the factors that affect the fusion-fission balance. Fission is a general stress response of cells, and in the case of yeast this response appears to be prosurvival. At the same time, even under normal conditions yeast mitochondria undergo continuous cycles of fusion and fission. This seems to be a futile cycle and also expensive from the energy point of view. Why does it exist? Benefits might be the same as in the case of sexual reproduction. Indeed, mixing and separating of mitochondrial content allows mitochondrial DNA to segregate and recombine randomly, leading to high variation in the numbers of mutations per individual mitochondrion. This opens a possibility for effective purifying selection-elimination of mitochondria highly contaminated by deleterious mutations. The beneficial action presumes a mechanism for removal of defective mitochondria. We argue that selective mitochondrial autophagy or asymmetrical distribution of mitochondria during cell division could be at the core of such mechanism.
24
KUROIWA, TSUNEYOSHI, MAKOTO FUJIE, and HARUKO KUROIWA. "Studies on the Behavior of Mitochondrial DNA." Journal of Cell Science 101, no. 3 (March 1, 1992): 483–93. http://dx.doi.org/10.1242/jcs.101.3.483.
Full textAbstract:
The fate of mitochondrial nuclei (known as nucleoids or mt-nuclei), which contain extremely small amounts of DNA, was followed in thin sections of the root meristem of Pelargonium zonale by embedding of samples in Technovit 7100 resin and double staining with 4′-6-diamidino-2-phenylindole (DAPI) and acridine orange, in combination with light-microscopic autoradiography and microphotometry. The synthesis of cell-nuclear DNA and cell division occurs actively in the root meristem, between 150 μm and 700 μm from the tip of the root. For simplicity, cells in S phase in the cortex were selected for main analysis as the model system for examination of cell proliferation. It is estimated, on the basis of the length of the cells in longitudinal median sections, that the cells in the cortex, which are generated in the area just above the quiescent center (QC) about 150 μm from the tip, enter the elongation zone after at least five divisions. In the entire cortex, individual cells in S phase have approximately 230 mitochondria that each contain one mt-nucleus. The observation suggests that individual mitochondria divide once per mitotic cycle in the entire region of the meristem. By contrast, on the basis of incorporation of [3H]thymidine into mt-nuclei, the synthesis of mitochondrial DNA (mtDNA) occurs independently of the mitotic cycle in a restricted region just above the QC. Fluorimetry, using a video-intensified microscope photon-counting system (VIMPICS), revealed that the mtDNA content per mt-nucleus in the cells just above QC, where the synthesis of mtDNA is active, corresponds to approximately 3000 kilobase pairs (kbp) but, in the meristematic cells just below the elongation zone of the root it falls to less than 170 kbp. These findings strongly suggest that the amount of mtDNA per mitochondrion which has been synthesized in the region just above the QC is reduced stepwise as a result of continuous divisions of mitochondria in the absence of the synthesis of mtDNA. This phenomenon would explain why differentiated cells with a large vacuole in the elongation zone have mitochondria that contain only extremely small amounts of mtDNA.
25
Sharma, Priyanka, and Harini Sampath. "Mitochondrial DNA Integrity: Role in Health and Disease." Cells 8, no. 2 (January 29, 2019): 100. http://dx.doi.org/10.3390/cells8020100.
Full textAbstract:
As the primary cellular location for respiration and energy production, mitochondria serve in a critical capacity to the cell. Yet, by virtue of this very function of respiration, mitochondria are subject to constant oxidative stress that can damage one of the unique features of this organelle, its distinct genome. Damage to mitochondrial DNA (mtDNA) and loss of mitochondrial genome integrity is increasingly understood to play a role in the development of both severe early-onset maladies and chronic age-related diseases. In this article, we review the processes by which mtDNA integrity is maintained, with an emphasis on the repair of oxidative DNA lesions, and the cellular consequences of diminished mitochondrial genome stability.
26
Krishnan, Kim J., and Doug M. Turnbull. "Mitochondrial DNA and genetic disease." Essays in Biochemistry 47 (June 14, 2010): 139–51. http://dx.doi.org/10.1042/bse0470139.
Full textAbstract:
From their very beginning to the present day, mitochondria have evolved to become a crucial organelle within the cell. The mitochondrial genome encodes only 37 genes, but its compact structure and minimal redundancy results in mutations on the mitochondrial genome being an important cause of genetic disease. In the present chapter we describe the up-to-date knowledge about mitochondrial DNA structure and function, and describe some of the consequences of defective function including disease and aging.
27
Falkenberg, Maria. "Mitochondrial DNA replication in mammalian cells: overview of the pathway." Essays in Biochemistry 62, no. 3 (June 7, 2018): 287–96. http://dx.doi.org/10.1042/ebc20170100.
Full textAbstract:
Mammalian mitochondria contain multiple copies of a circular, double-stranded DNA genome and a dedicated DNA replication machinery is required for its maintenance. Many disease-causing mutations affect mitochondrial replication factors and a detailed understanding of the replication process may help to explain the pathogenic mechanisms underlying a number of mitochondrial diseases. We here give a brief overview of DNA replication in mammalian mitochondria, describing our current understanding of this process and some unanswered questions remaining.
28
Gordon, Donna M., and Janine Hertzog Santos. "The Emerging Role of Telomerase Reverse Transcriptase in Mitochondrial DNA Metabolism." Journal of Nucleic Acids 2010 (2010): 1–7. http://dx.doi.org/10.4061/2010/390791.
Full textAbstract:
Telomerase is a reverse transcriptase specialized in telomere synthesis. The enzyme is primarily nuclear where it elongates telomeres but recent reports have shown that it also localizes to mitochondria. The function of TERT in mitochondria is largely unknown but the available findings point to a role in mitochondrial DNA metabolism. This paper discusses the available data on mitochondrial telomerase with particular emphasis on its effects upon the organellar DNA.
29
Yang, Xuan, Ruoyu Zhang, Kiichi Nakahira, and Zhenglong Gu. "Mitochondrial DNA Mutation, Diseases, and Nutrient-Regulated Mitophagy." Annual Review of Nutrition 39, no. 1 (August 21, 2019): 201–26. http://dx.doi.org/10.1146/annurev-nutr-082018-124643.
Full textAbstract:
A wide spectrum of human diseases, including cancer, neurodegenerative diseases, and metabolic disorders, have been shown to be associated with mitochondrial dysfunction through multiple molecular mechanisms. Mitochondria are particularly susceptible to nutrient deficiencies, and nutritional intervention is an essential way to maintain mitochondrial homeostasis. Recent advances in genetic manipulation and next-generation sequencing reveal the crucial roles of mitochondrial DNA (mtDNA) in various pathophysiological conditions. Mitophagy, a term coined to describe autophagy that targets dysfunctional mitochondria, has emerged as an important cellular process to maintain mitochondrial homeostasis and has been shown to be regulated by various nutrients and nutritional stresses. Given the high prevalence of mtDNA mutations in humans and their impact on mitochondrial function, it is important to investigate the mechanisms that regulate mtDNA mutation. Here, we discuss mitochondrial genetics and mtDNA mutations and their implications for human diseases. We also examine the role of mitophagy as a therapeutic target, highlighting how nutrients may eliminate mtDNA mutations through mitophagy.
30
Hirota, Yuko, Dongchon Kang, and Tomotake Kanki. "The Physiological Role of Mitophagy: New Insights into Phosphorylation Events." International Journal of Cell Biology 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/354914.
Full textAbstract:
Mitochondria play an essential role in oxidative phosphorylation, fatty acid oxidation, and the regulation of apoptosis. However, this organelle also produces reactive oxygen species (ROS) that continually inflict oxidative damage on mitochondrial DNA, proteins, and lipids, which causes further production of ROS. To oppose this oxidative stress, mitochondria possess quality control systems that include antioxidant enzymes and the repair or degradation of damaged mitochondrial DNA and proteins. If the oxidative stress exceeds the capacity of the mitochondrial quality control system, it seems that autophagy degrades the damaged mitochondria to maintain cellular homeostasis. Indeed, recent evidence from yeast to mammals indicates that the autophagy-dependent degradation of mitochondria (mitophagy) contributes to eliminate dysfunctional, aged, or excess mitochondria. In this paper, we describe the molecular processes and regulatory mechanisms of mitophagy in yeast and mammalian cells.
31
Manev, Hari, and Svetlana Dzitoyeva. "Progress in mitochondrial epigenetics." BioMolecular Concepts 4, no. 4 (August 1, 2013): 381–89. http://dx.doi.org/10.1515/bmc-2013-0005.
Full textAbstract:
AbstractMitochondria, intracellular organelles with their own genome, have been shown capable of interacting with epigenetic mechanisms in at least four different ways. First, epigenetic mechanisms that regulate the expression of nuclear genome influence mitochondria by modulating the expression of nuclear-encoded mitochondrial genes. Second, a cell-specific mitochondrial DNA content (copy number) and mitochondrial activity determine the methylation pattern of nuclear genes. Third, mitochondrial DNA variants influence the nuclear gene expression patterns and the nuclear DNA (ncDNA) methylation levels. Fourth and most recent line of evidence indicates that mitochondrial DNA similar to ncDNA also is subject to epigenetic modifications, particularly by the 5-methylcytosine and 5-hydroxymethylcytosine marks. The latter interaction of mitochondria with epigenetics has been termed ‘mitochondrial epigenetics’. Here we summarize recent developments in this particular area of epigenetic research. Furthermore, we propose the term ‘mitoepigenetics’ to include all four above-noted types of interactions between mitochondria and epigenetics, and we suggest a more restricted usage of the term ‘mitochondrial epigenetics’ for molecular events dealing solely with the intra-mitochondrial epigenetics and the modifications of mitochondrial genome.
32
Lin, Tsu-Kung, Shang-Der Chen, Yao-Chung Chuang, Min-Yu Lan, Jiin-Haur Chuang, Pei-Wen Wang, Te-Yao Hsu, et al. "Mitochondrial Transfer of Wharton’s Jelly Mesenchymal Stem Cells Eliminates Mutation Burden and Rescues Mitochondrial Bioenergetics in Rotenone-Stressed MELAS Fibroblasts." Oxidative Medicine and Cellular Longevity 2019 (May 22, 2019): 1–17. http://dx.doi.org/10.1155/2019/9537504.
Full textAbstract:
Wharton’s jelly mesenchymal stem cells (WJMSCs) transfer healthy mitochondria to cells harboring a mitochondrial DNA (mtDNA) defect. Mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the major subgroups of mitochondrial diseases, caused by the mt.3243A>G point mutation in the mitochondrial tRNALeu(UUR) gene. The specific aim of the study is to investigate whether WJMSCs exert therapeutic effect for mitochondrial dysfunction in cells of MELAS patient through donating healthy mitochondria. We herein demonstrate that WJMSCs transfer healthy mitochondria into rotenone-stressed fibroblasts of a MELAS patient, thereby eliminating mutation burden and rescuing mitochondrial functions. In the coculture system in vitro study, WJMSCs transferred healthy mitochondria to rotenone-stressed MELAS fibroblasts. By inhibiting actin polymerization to block tunneling nanotubes (TNTs), the WJMSC-conducted mitochondrial transfer was abrogated. After mitochondrial transfer, the mt.3243A>G mutation burden of MELAS fibroblasts was reduced to an undetectable level, with long-term retention. Sequencing results confirmed that the transferred mitochondria were donated from WJMSCs. Furthermore, mitochondrial transfer of WJMSCs to MELAS fibroblasts improves mitochondrial functions and cellular performance, including protein translation of respiratory complexes, ROS overexpression, mitochondrial membrane potential, mitochondrial morphology and bioenergetics, cell proliferation, mitochondrion-dependent viability, and apoptotic resistance. This study demonstrates that WJMSCs exert bioenergetic therapeutic effects through mitochondrial transfer. This finding paves the way for the development of innovative treatments for MELAS and other mitochondrial diseases.
33
Rivas-García, Lorenzo, José Luis Quiles, Alfonso Varela-López, Francesca Giampieri, Maurizio Battino, Jörg Bettmer, María Montes-Bayón, Juan Llopis, and Cristina Sánchez-González. "Ultra-Small Iron Nanoparticles Target Mitochondria Inducing Autophagy, Acting on Mitochondrial DNA and Reducing Respiration." Pharmaceutics 13, no. 1 (January 12, 2021): 90. http://dx.doi.org/10.3390/pharmaceutics13010090.
Full textAbstract:
The application of metallic nanoparticles (materials with size at least in one dimension ranging from 1 to 100 nm) as a new therapeutic tool will improve the diagnosis and treatment of diseases. The mitochondria could be a therapeutic target to treat pathologies whose origin lies in mitochondrial dysfunctions or whose progression is dependent on mitochondrial function. We aimed to study the subcellular distribution of 2–4 nm iron nanoparticles and its effect on mitochondrial DNA (mtDNA), mitochondrial function, and autophagy in colorectal cell lines (HT-29). Results showed that when cells were exposed to ultra-small iron nanoparticles, their subcellular fate was mainly mitochondria, affecting its respiratory and glycolytic parameters, inducing the migration of the cellular state towards quiescence, and promoting and triggering the autophagic process. These effects support the potential use of nanoparticles as therapeutic agents using mitochondria as a target for cancer and other treatments for mitochondria-dependent pathologies.
34
Lucini, Chantal B., and Ralf J. Braun. "Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies." Biomedicines 9, no. 4 (April 2, 2021): 376. http://dx.doi.org/10.3390/biomedicines9040376.
Full textAbstract:
In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.
35
Dan, Xiuli, Mansi Babbar, Anthony Moore, Noah Wechter, Jingyan Tian, Joy G. Mohanty, Deborah L. Croteau, and Vilhelm A. Bohr. "DNA damage invokes mitophagy through a pathway involving Spata18." Nucleic Acids Research 48, no. 12 (May 26, 2020): 6611–23. http://dx.doi.org/10.1093/nar/gkaa393.
Full textAbstract:
Abstract Mitochondria are vital for cellular energy supply and intracellular signaling after stress. Here, we aimed to investigate how mitochondria respond to acute DNA damage with respect to mitophagy, which is an important mitochondrial quality control process. Our results show that mitophagy increases after DNA damage in primary fibroblasts, murine neurons and Caenorhabditis elegans neurons. Our results indicate that modulation of mitophagy after DNA damage is independent of the type of DNA damage stimuli used and that the protein Spata18 is an important player in this process. Knockdown of Spata18 suppresses mitophagy, disturbs mitochondrial Ca2+ homeostasis, affects ATP production, and attenuates DNA repair. Importantly, mitophagy after DNA damage is a vital cellular response to maintain mitochondrial functions and DNA repair.
36
Vianello, Caterina, Veronica Cocetta, Federico Caicci, Francesco Boldrin, Monica Montopoli, Andrea Martinuzzi, Valerio Carelli, and Marta Giacomello. "Interaction Between Mitochondrial DNA Variants and Mitochondria/Endoplasmic Reticulum Contact Sites: A Perspective Review." DNA and Cell Biology 39, no. 8 (August 1, 2020): 1431–43. http://dx.doi.org/10.1089/dna.2020.5614.
Full text
37
Gurdon, Csanad, Zora Svab, Yaping Feng, Dibyendu Kumar, and Pal Maliga. "Cell-to-cell movement of mitochondria in plants." Proceedings of the National Academy of Sciences 113, no. 12 (March 7, 2016): 3395–400. http://dx.doi.org/10.1073/pnas.1518644113.
Full textAbstract:
We report cell-to-cell movement of mitochondria through a graft junction. Mitochondrial movement was discovered in an experiment designed to select for chloroplast transfer from Nicotiana sylvestris into Nicotiana tabacum cells. The alloplasmic N. tabacum line we used carries Nicotiana undulata cytoplasmic genomes, and its flowers are male sterile due to the foreign mitochondrial genome. Thus, rare mitochondrial DNA transfer from N. sylvestris to N. tabacum could be recognized by restoration of fertile flower anatomy. Analyses of the mitochondrial genomes revealed extensive recombination, tentatively linking male sterility to orf293, a mitochondrial gene causing homeotic conversion of anthers into petals. Demonstrating cell-to-cell movement of mitochondria reconstructs the evolutionary process of horizontal mitochondrial DNA transfer and enables modification of the mitochondrial genome by DNA transmitted from a sexually incompatible species. Conversion of anthers into petals is a visual marker that can be useful for mitochondrial transformation.
38
Hadjivasiliou, Zena, Andrew Pomiankowski, Robert M. Seymour, and Nick Lane. "Selection for mitonuclear co-adaptation could favour the evolution of two sexes." Proceedings of the Royal Society B: Biological Sciences 279, no. 1734 (December 7, 2011): 1865–72. http://dx.doi.org/10.1098/rspb.2011.1871.
Full textAbstract:
Mitochondria are descended from free-living bacteria that were engulfed by another cell between one and a half to two billion years ago. A redistribution of DNA led to most genetic information being lost or transferred to a large central genome in the nucleus, leaving a residual genome in each mitochondrion. Oxidative phosphorylation, the most critical function of mitochondria, depends on the functional compatibility of proteins encoded by both the nucleus and mitochondria. We investigate whether selection for adaptation between the nuclear and mitochondrial genomes (mitonuclear co-adaptation) could, in principle, have promoted uniparental inheritance of mitochondria and thereby the evolution of two mating types or sexes. Using a mathematical model, we explore the importance of the radical differences in ploidy levels, sexual and asexual modes of inheritance, and mutation rates of the nucleus and mitochondria. We show that the major features of mitochondrial inheritance, notably uniparental inheritance and bottlenecking, enhance the co-adaptation of mitochondrial and nuclear genes and therefore improve fitness. We conclude that, under a wide range of conditions, selection for mitonuclear co-adaptation favours the evolution of two distinct mating types or sexes in sexual species.
39
Sedman, Tiina, Silja Kuusk, Sirje Kivi, and Juhan Sedman. "A DNA Helicase Required for Maintenance of the Functional Mitochondrial Genome in Saccharomyces cerevisiae." Molecular and Cellular Biology 20, no. 5 (March 1, 2000): 1816–24. http://dx.doi.org/10.1128/mcb.20.5.1816-1824.2000.
Full textAbstract:
ABSTRACT A novel DNA helicase, a homolog of several prokaryotic helicases, including Escherichia coli Rep and UvrD proteins, is encoded by the Saccharomyces cerevisiae nuclear genome open reading frame YOL095c on the chromosome XV. Our data demonstrate that the helicase is localized in the yeast mitochondria and is loosely associated with the mitochondrial inner membrane during biochemical fractionation. The sequence of the C-terminal end of the 80-kDa helicase protein is similar to a typical N-terminal mitochondrial targeting signal; deletions and point mutations in this region abolish transport of the protein into mitochondria. The C-terminal signal sequence of the helicase targets a heterologous carrier protein into mitochondria in vivo. The purified recombinant protein can unwind duplex DNA molecules in an ATP-dependent manner. The helicase is required for the maintenance of the functional ([rho +]) mitochondrial genome on both fermentable and nonfermentable carbon sources. However, the helicase is not essential for the maintenance of several defective ([rho −]) mitochondrial genomes. We also demonstrate that the helicase is not required for transcription in mitochondria.
40
Temelie, Mihaela, Diana Iulia Savu, and Nicoleta Moisoi. "Intracellular and Intercellular Signalling Mechanisms following DNA Damage Are Modulated By PINK1." Oxidative Medicine and Cellular Longevity 2018 (June 27, 2018): 1–15. http://dx.doi.org/10.1155/2018/1391387.
Full textAbstract:
Impaired mitochondrial function and accumulation of DNA damage have been recognized as hallmarks of age-related diseases. Mitochondrial dysfunction initiates protective signalling mechanisms coordinated at nuclear level particularly by modulating transcription of stress signalling factors. In turn, cellular response to DNA lesions comprises a series of interconnected complex protective pathways, which require the energetic and metabolic support of the mitochondria. These are involved in intracellular as well as in extracellular signalling of damage. Here, we have initiated a study that addresses how mitochondria-nucleus communication may occur in conditions of combined mitochondrial dysfunction and genotoxic stress and what are the consequences of this interaction on the cell system. In this work, we used cells deficient for PINK1, a mitochondrial kinase involved in mitochondrial quality control whose loss of function leads to the accumulation of dysfunctional mitochondria, challenged with inducers of DNA damage, namely, ionizing radiation and the radiomimetic bleomycin. Combined stress at the level of mitochondria and the nucleus impairs both mitochondrial and nuclear functions. Our findings revealed exacerbated sensibility to genotoxic stress in PINK1-deficient cells. The same cells showed an impaired induction of bystander phenomena following stress insults. However, these cells responded adaptively when a challenge dose was applied subsequently to a low-dose treatment to the cells. The data demonstrates that PINK1 modulates intracellular and intercellular signalling pathways, particularly adaptive responses and transmission of bystander signalling, two facets of the cell-protective mechanisms against detrimental agents.
41
Pinter, Stefan F., Sarah D. Aubert, and Virginia A. Zakian. "The Schizosaccharomyces pombe Pfh1p DNA Helicase Is Essential for the Maintenance of Nuclear and Mitochondrial DNA." Molecular and Cellular Biology 28, no. 21 (August 25, 2008): 6594–608. http://dx.doi.org/10.1128/mcb.00191-08.
Full textAbstract:
ABSTRACT Schizosaccharomyces pombe Pfh1p is an essential member of the Pif family of 5′-3′ DNA helicases. The two Saccharomyces cerevisiae homologs, Pif1p and Rrm3p, function in nuclear DNA replication, telomere length regulation, and mitochondrial genome integrity. We demonstrate here the existence of multiple Pfh1p isoforms that localized to either nuclei or mitochondria. The catalytic activity of Pfh1p was essential in both cellular compartments. The absence of nuclear Pfh1p resulted in G2 arrest and accumulation of DNA damage foci, a finding suggestive of an essential role in DNA replication. Exogenous DNA damage resulted in localization of Pfh1p to DNA damage foci, suggesting that nuclear Pfh1p also functions in DNA repair. The absence of mitochondrial Pfh1p caused rapid depletion of mitochondrial DNA. Despite localization to nuclei and mitochondria in S. pombe, neither of the S. cerevisiae homologs, nor human PIF1, suppressed the lethality of pfh1Δ cells. However, the essential nuclear function of Pfh1p could be supplied by Rrm3p. Expression of Rrm3p suppressed the accumulation of DNA damage foci but not the hydroxyurea sensitivity of cells depleted of nuclear Pfh1p. Together, these data demonstrate that Pfh1p has essential roles in the replication of both nuclear and mitochondrial DNA.
42
Qian, Wei, Namrata Kumar, Vera Roginskaya, Elise Fouquerel, Patricia L. Opresko, Sruti Shiva, Simon C. Watkins, Dmytro Kolodieznyi, Marcel P. Bruchez, and Bennett Van Houten. "Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction." Proceedings of the National Academy of Sciences 116, no. 37 (August 26, 2019): 18435–44. http://dx.doi.org/10.1073/pnas.1910574116.
Full textAbstract:
Reactive oxygen species (ROS) play important roles in aging, inflammation, and cancer. Mitochondria are an important source of ROS; however, the spatiotemporal ROS events underlying oxidative cellular damage from dysfunctional mitochondria remain unresolved. To this end, we have developed and validated a chemoptogenetic approach that uses a mitochondrially targeted fluorogen-activating peptide (Mito-FAP) to deliver a photosensitizer MG-2I dye exclusively to this organelle. Light-mediated activation (660 nm) of the Mito-FAP–MG-2I complex led to a rapid loss of mitochondrial respiration, decreased electron transport chain complex activity, and mitochondrial fragmentation. Importantly, one round of singlet oxygen produced a persistent secondary wave of mitochondrial superoxide and hydrogen peroxide lasting for over 48 h after the initial insult. By following ROS intermediates, we were able to detect hydrogen peroxide in the nucleus through ratiometric analysis of the oxidation of nuclear cysteine residues. Despite mitochondrial DNA (mtDNA) damage and nuclear oxidative stress induced by dysfunctional mitochondria, there was a lack of gross nuclear DNA strand breaks and apoptosis. Targeted telomere analysis revealed fragile telomeres and telomere loss as well as 53BP1-positive telomere dysfunction-induced foci (TIFs), indicating that DNA double-strand breaks occurred exclusively in telomeres as a direct consequence of mitochondrial dysfunction. These telomere defects activated ataxia-telangiectasia mutated (ATM)-mediated DNA damage repair signaling. Furthermore, ATM inhibition exacerbated the Mito-FAP–induced mitochondrial dysfunction and sensitized cells to apoptotic cell death. This profound sensitivity of telomeres through hydrogen peroxide induced by dysregulated mitochondria reveals a crucial mechanism of telomere–mitochondria communication underlying the pathophysiological role of mitochondrial ROS in human diseases.
43
Konstantinov, Yu M., A. Dietrich, F. Weber-Lotfi, N. Ibrahim, E. S. Klimenko, V. I. Tarasenko, T. A. Bolotova, and M. V. Koulintchenko. "DNA import into mitochondria." Biochemistry (Moscow) 81, no. 10 (October 2016): 1044–56. http://dx.doi.org/10.1134/s0006297916100035.
Full text
44
Erxleben, Andrea. "Mitochondria-Targeting Anticancer Metal Complexes." Current Medicinal Chemistry 26, no. 4 (April 1, 2019): 694–728. http://dx.doi.org/10.2174/0929867325666180307112029.
Full textAbstract:
Background: Since the serendipitous discovery of the antitumor activity of cisplatin there has been a continuous surge in studies aimed at the development of new cytotoxic metal complexes. While the majority of these complexes have been designed to interact with nuclear DNA, other targets for anticancer metallodrugs attract increasing interest. In cancer cells the mitochondrial metabolism is deregulated. Impaired apoptosis, insensitivity to antigrowth signals and unlimited proliferation have been linked to mitochondrial dysfunction. It is therefore not surprising that mitochondria have emerged as a major target for cancer therapy. Mitochondria-targeting agents are able to bypass resistance mechanisms and to (re-) activate cell-death programs. Methods: Web-based literature searching tools such as SciFinder were used to search for reports on cytotoxic metal complexes that are taken up by the mitochondria and interact with mitochondrial DNA or mitochondrial proteins, disrupt the mitochondrial membrane potential, facilitate mitochondrial membrane permeabilization or activate mitochondria-dependent celldeath signaling by unbalancing the cellular redox state. Included in the search were publications investigating strategies to selectively accumulate metallodrugs in the mitochondria. Results: This review includes 241 references on antimitochondrial metal complexes, the use of mitochondria-targeting carrier ligands and the formation of lipophilic cationic complexes. Conclusion: Recent developments in the design, cytotoxic potency, and mechanistic understanding of antimitochondrial metal complexes, in particular of cyclometalated Au, Ru, Ir and Pt complexes, Ru polypyridine complexes and Au-N-heterocyclic carbene and phosphine complexes are summarized and discussed.
45
Eyre-Walker, Adam. "Do mitochondria recombine in humans?" Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 355, no. 1403 (November 29, 2000): 1573–80. http://dx.doi.org/10.1098/rstb.2000.0718.
Full textAbstract:
Until very recently, mitochondria were thought to be clonally inherited through the maternal line in most higher animals. However, three papers published in 2000 claimed population–genetic evidence of recombination in human mitochondrial DNA. Here I review the current state of the debate. I review the evidence for the two main pathways by which recombination might occur: through paternal leakage and via a mitochondrial DNA sequence in the nuclear genome. There is no strong evidence for either pathway, although paternal leakage seems a definite possibility. However, the population–genetic evidence, although not conclusive, is strongly suggestive of recombination in mitochondrial DNA. The implications of non–clonality for our understanding of human and mitochondrial evolution are discussed.
46
Mancuso, Michelangelo, Daniele Orsucci, Gabiele Siciliano, and Luigi Murri. "Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?" Current Alzheimer Research 5, no. 5 (October 1, 2008): 457–68. http://dx.doi.org/10.2174/156720508785908946.
Full text
47
Piantadosi, Claude A., Martha Sue Carraway, Karen E. Welty-Wolf, and Hagir B. Suliman. "OXIDATIVE DAMAGE OF MITOCHONDRIA AND MITOCHONDRIAL DNA IN SEPSIS." Shock 21, Supplement (March 2004): 57. http://dx.doi.org/10.1097/00024382-200403001-00228.
Full text
48
Croteau, Deborah L., Marie L. Rossi, Chandrika Canugovi, Jane Tian, Peter Sykora, Mahesh Ramamoorthy, ZhengMing Wang, et al. "RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity." Aging Cell 11, no. 3 (March 2, 2012): 456–66. http://dx.doi.org/10.1111/j.1474-9726.2012.00803.x.
Full text
49
Zheng, Ningning, Dan Wei, Bo Dai, Lanyan Zheng, Mingyi Zhao, Na Xin, Zhihong Chi, et al. "Mitochondrial Genome Encoded Proteins Expression Disorder, the Possible Mechanism of the Heart Disease in Metabolic Syndrome." Cellular Physiology and Biochemistry 43, no. 3 (2017): 959–68. http://dx.doi.org/10.1159/000481649.
Full textAbstract:
Background/Aims: The direct consequence of metabolic syndrome (MS) is the increased morbidity and mortality caused by the heart disease. We tried to explain why the heart is more severely damaged during MS from the point of mitochondria, the center of cellular metabolism. Methods: 1. The classic diet induced MS rat model was used to observe the morphological changes of mitochondria by transmission electron microscope (TEM); 2. The expression of mitochondrial DNA (mt-DNA) encoded proteins was observed by immunohistochemistry and Western blot; 3. The expression of mitochondrial ribosomal proteins (MRPs) was observed by real-time PCR. Results: 1. The mitochondrial volume increased but the number was normal in myocardial cells of the MS rats. But in the hepatocytes and skeletal muscle cells, the mitochondrial number decreased; 2.The mt-DNA encoded protein cytochrome b increased significantly in heart but decreased in liver and the ATPase6 increased in liver but decreased in heart of the MS rats; 3. The mRNA levels of MRPS23, MRPL27, MRPL45 and MRPL48 elevated in heart but down-regulated in liver of the MS rats. Conclusion: The morphologic and functional alterations of mitochondrion in MS were tissue specific. Heart displays a distinctive pattern of mitochondrial metabolic status compared with other tissues.
50
Almeida, Andréa M., Clélia R. A. Bertoncini, Jiri Borecký, Nadja C. Souza-Pinto, and Aníbal E. Vercesi. "Mitochondrial DNA damage associated with lipid peroxidation of the mitochondrial membrane induced by Fe2+-citrate." Anais da Academia Brasileira de Ciências 78, no. 3 (September 2006): 505–14. http://dx.doi.org/10.1590/s0001-37652006000300010.
Full textAbstract:
Iron imbalance/accumulation has been implicated in oxidative injury associated with many degenerative diseases such as hereditary hemochromatosis, beta-thalassemia, and Friedreich's ataxia. Mitochondria are particularly sensitive to iron-induced oxidative stress - high loads of iron cause extensive lipid peroxidation and membrane permeabilization in isolated mitochondria. Here we detected and characterized mitochondrial DNA damage in isolated rat liver mitochondria exposed to a Fe2+-citrate complex, a small molecular weight complex. Intense DNA fragmentation was induced after the incubation of mitochondria with the iron complex. The detection of 3' phosphoglycolate ends at the mtDNA strand breaks by a 32P-postlabeling assay, suggested the involvement of hydroxyl radical in the DNA fragmentation induced by Fe2+-citrate. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine also suggested that Fe2+-citrate-induced oxidative stress causes mitochondrial DNA damage. In conclusion, our results show that iron-mediated lipid peroxidation was associated with intense mtDNA damage derived from the direct attack of reactive oxygen species.