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International Journal of Molecular... Jun 2019As with all organisms that must organize and condense their DNA to fit within the limited volume of a cell or a nucleus, mammalian mitochondrial DNA (mtDNA) is packaged... (Review)
Review
As with all organisms that must organize and condense their DNA to fit within the limited volume of a cell or a nucleus, mammalian mitochondrial DNA (mtDNA) is packaged into nucleoprotein structures called nucleoids. In this study, we first introduce the general modes of DNA compaction, especially the role of the nucleoid-associated proteins (NAPs) that structure the bacterial chromosome. We then present the mitochondrial nucleoid and the main factors responsible for packaging of mtDNA: ARS- (autonomously replicating sequence-) binding factor 2 protein (Abf2p) in yeast and mitochondrial transcription factor A (TFAM) in mammals. We summarize the single-molecule manipulation experiments on mtDNA compaction and visualization of mitochondrial nucleoids that have led to our current knowledge on mtDNA compaction. Lastly, we discuss the possible regulatory role of DNA packaging by TFAM in DNA transactions such as mtDNA replication and transcription.
Topics: Animals; DNA Replication; DNA, Mitochondrial; Humans; Mammals; Mitochondrial Proteins; Nucleic Acid Conformation; Saccharomyces cerevisiae
PubMed: 31195723
DOI: 10.3390/ijms20112770 -
Mitochondrial DNA replication and repair defects: Clinical phenotypes and therapeutic interventions.Biochimica Et Biophysica Acta.... Jun 2022Mitochondria is a unique cellular organelle involved in multiple cellular processes and is critical for maintaining cellular homeostasis. This semi-autonomous organelle... (Review)
Review
Mitochondria is a unique cellular organelle involved in multiple cellular processes and is critical for maintaining cellular homeostasis. This semi-autonomous organelle contains its circular genome - mtDNA (mitochondrial DNA), that undergoes continuous cycles of replication and repair to maintain the mitochondrial genome integrity. The majority of the mitochondrial genes, including mitochondrial replisome and repair genes, are nuclear-encoded. Although the repair machinery of mitochondria is quite efficient, the mitochondrial genome is highly susceptible to oxidative damage and other types of exogenous and endogenous agent-induced DNA damage, due to the absence of protective histones and their proximity to the main ROS production sites. Mutations in replication and repair genes of mitochondria can result in mtDNA depletion and deletions subsequently leading to mitochondrial genome instability. The combined action of mutations and deletions can result in compromised mitochondrial genome maintenance and lead to various mitochondrial disorders. Here, we review the mechanism of mitochondrial DNA replication and repair process, key proteins involved, and their altered function in mitochondrial disorders. The focus of this review will be on the key genes of mitochondrial DNA replication and repair machinery and the clinical phenotypes associated with mutations in these genes.
Topics: DNA Replication; DNA, Mitochondrial; Humans; Mitochondria; Mitochondrial Diseases; Phenotype
PubMed: 35341749
DOI: 10.1016/j.bbabio.2022.148554 -
Biochemistry. Biokhimiia Oct 2016Mitochondrial DNA (mtDNA) in cells is organized in nucleoids containing DNA and various proteins. This review discusses questions of organization and structural dynamics... (Review)
Review
Mitochondrial DNA (mtDNA) in cells is organized in nucleoids containing DNA and various proteins. This review discusses questions of organization and structural dynamics of nucleoids as well as their protein components. The structures of mt-nucleoid from different organisms are compared. The currently accepted model of nucleoid organization is described and questions needing answers for better understanding of the fine mechanisms of the mitochondrial genetic apparatus functioning are discussed.
Topics: Animals; DNA, Mitochondrial; Genome, Mitochondrial; Humans; Mitochondria; Mitochondrial Proteins
PubMed: 27908231
DOI: 10.1134/S0006297916100047 -
International Journal of Molecular... Sep 2022Mitochondria are the only organelles, along with the nucleus, that have their own DNA. Mitochondrial DNA (mtDNA) is a double-stranded circular molecule of ~16.5 kbp that... (Review)
Review
Mitochondria are the only organelles, along with the nucleus, that have their own DNA. Mitochondrial DNA (mtDNA) is a double-stranded circular molecule of ~16.5 kbp that can exist in multiple copies within the organelle. Both strands are translated and encode for 22 tRNAs, 2 rRNAs, and 13 proteins. mtDNA molecules are anchored to the inner mitochondrial membrane and, in association with proteins, form a structure called nucleoid, which exerts a structural and protective function. Indeed, mitochondria have evolved mechanisms necessary to protect their DNA from chemical and physical lesions such as DNA repair pathways similar to those present in the nucleus. However, there are mitochondria-specific mechanisms such as rapid mtDNA turnover, fission, fusion, and mitophagy. Nevertheless, mtDNA mutations may be abundant in somatic tissue due mainly to the proximity of the mtDNA to the oxidative phosphorylation (OXPHOS) system and, consequently, to the reactive oxygen species (ROS) formed during ATP production. In this review, we summarise the most common types of mtDNA lesions and mitochondria repair mechanisms. The second part of the review focuses on the physiological role of mtDNA damage in ageing and the effect of mtDNA mutations in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Considering the central role of mitochondria in maintaining cellular homeostasis, the analysis of mitochondrial function is a central point for developing personalised medicine.
Topics: Adenosine Triphosphate; DNA Damage; DNA Repair; DNA, Mitochondrial; Humans; Mitochondrial Diseases; Neurodegenerative Diseases; Reactive Oxygen Species
PubMed: 36232693
DOI: 10.3390/ijms231911391 -
Mitochondrial DNA. Part A, DNA Mapping,... Jan 2017Mitochondrial DNA has the characteristic of quick evolution, matrilineal inheritance, and simple molecular structure, and it serves as the most used marker for molecular... (Review)
Review
Mitochondrial DNA has the characteristic of quick evolution, matrilineal inheritance, and simple molecular structure, and it serves as the most used marker for molecular study. As an important role of genomics, studying it can help understand the origins, history, and adaptation of domestication. Because of its wide spread popularity, chicken is one of the important domestic animals, which provides humans with a stable source of protein, including both meat and eggs. This article reviews recent studies of chicken mitochondrial DNA. Mitochondrial D-loop and mitochondrial genomics pinpoint the geographic origins of the domestic chicken which was multiple origins; moreover, the mitochondria gene mutation has an association with high-altitude adaptation and the mitochondria-associated diseases' study in poultry is not performed.
Topics: Animals; Animals, Domestic; Avian Proteins; Chickens; DNA, Mitochondrial; Promoter Regions, Genetic
PubMed: 26680506
DOI: 10.3109/19401736.2015.1106526 -
Biochimica Et Biophysica Acta. Gene... Mar 2019Correct expression of the mitochondrially-encoded genes is critical for the production of the components of the oxidative phosphorylation machinery. Post-transcriptional... (Review)
Review
Correct expression of the mitochondrially-encoded genes is critical for the production of the components of the oxidative phosphorylation machinery. Post-transcriptional modifications of mitochondrial transcripts have been emerging as an important regulatory feature of mitochondrial gene expression. Here we review the current knowledge on how the mammalian mitochondrial epitranscriptome participates in regulating mitochondrial homeostasis. In particular, we focus on the latest breakthroughs made towards understanding the roles of the modified nucleotides in mitochondrially-encoded ribosomal and transfer RNAs, the enzymes responsible for introducing these modifications and on recent transcriptome-wide studies reporting modifications to mitochondrial messenger RNAs. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Matthias Soller and Dr. Rupert Fray.
Topics: Animals; DNA, Mitochondrial; Epigenesis, Genetic; Humans; RNA Processing, Post-Transcriptional; Transcriptome
PubMed: 30529456
DOI: 10.1016/j.bbagrm.2018.11.005 -
Journal of Translational Medicine May 2023Recent evidence has shown significant roles of mitochondria-derived vesicles (MDVs) in mitochondrial quality control (MQC) system. Under mild stress condition, MDVs are... (Review)
Review
Recent evidence has shown significant roles of mitochondria-derived vesicles (MDVs) in mitochondrial quality control (MQC) system. Under mild stress condition, MDVs are formed to carry the malfunctioned mitochondrial components, such as mitochondrial DNA (mtDNA), peptides, proteins and lipids, to be eliminated to restore normal mitochondrial structure and functions. Under severe oxidative stress condition, mitochondrial dynamics (fission/fusion) and mitophagy are predominantly activated to rescue mitochondrial structure and functions. Additionally, MDVs generation can be also triggered as the major MQC machinery to cope with unhealthy mitochondria when mitophagy is unsuccessful for eliminating the damaged mitochondria or mitochondrial fission/fusion fail to recover the mitochondrial structure and functions. This review summarizes the current knowledge on MDVs and discuss their roles in physiologic and pathophysiologic conditions. In addition, the potential clinical relevance of MDVs in therapeutics and diagnostics of kidney stone disease (KSD) are emphasized.
Topics: Humans; Mitochondria; Oxidative Stress; DNA, Mitochondrial; Mitophagy; Kidney Calculi
PubMed: 37131163
DOI: 10.1186/s12967-023-04133-3 -
Journal of the American Association of... Sep 2021The mitochondrial genome, which contains all of the hereditary information within human mitochondria, consists of 16,569 base pairs of double-stranded DNA that encode 37...
The mitochondrial genome, which contains all of the hereditary information within human mitochondria, consists of 16,569 base pairs of double-stranded DNA that encode 37 genes. Pathogenic mutations of mitochondrial DNA (mtDNA) cause dysfunction of the respiratory chain and the process of oxidative phosphorylation (OXPHOS), leading to impaired adenosine triphosphate synthesis. Nuclear DNA (nDNA) mutations can affect structural subunits or assembly factors of one of the five OXPHOS complexes. Mitochondrial diseases are a heterogeneous group of disorders, ranging from mtDNA single-point mutations and large-scale deletions to mitochondrial depletion syndromes, resulting from nDNA pathogenic mutations. Manifestations of mitochondrial disease are multisystemic, and organs with substantial energy requirements are most typically affected. Mitochondrial disorders are progressive in nature, and prognosis is dependent on the organs involved and the rate and severity of disease progression. A multidisciplinary team approach is needed to monitor and manage disease sequelae.
Topics: DNA, Mitochondrial; Humans; Mitochondria; Mitochondrial Diseases; Mutation; Oxidative Phosphorylation
PubMed: 34491238
DOI: 10.1097/JXX.0000000000000646 -
Cells Feb 2022Mitochondria are primarily involved in cell bioenergetics, regulation of redox homeostasis, and cell death/survival signaling. An immunostimulatory property of... (Review)
Review
Mitochondria are primarily involved in cell bioenergetics, regulation of redox homeostasis, and cell death/survival signaling. An immunostimulatory property of mitochondria has also been recognized which is deployed through the extracellular release of entire or portioned organelle and/or mitochondrial DNA (mtDNA) unloading. Dynamic homo- and heterotypic interactions involving mitochondria have been described. Each type of connection has functional implications that eventually optimize mitochondrial activity according to the bioenergetic demands of a specific cell/tissue. Inter-organelle communications may also serve as molecular platforms for the extracellular release of mitochondrial components and subsequent ignition of systemic inflammation. Age-related chronic inflammation (inflamm-aging) has been associated with mitochondrial dysfunction and increased extracellular release of mitochondrial components-in particular, cell-free mtDNA. The close relationship between mitochondrial dysfunction and cellular senescence further supports the central role of mitochondria in the aging process and its related conditions. Here, we provide an overview of (1) the mitochondrial genetic system and the potential routes for generating and releasing mtDNA intermediates; (2) the pro-inflammatory pathways elicited by circulating mtDNA; (3) the participation of inter-organelle contacts to mtDNA homeostasis; and (4) the link of these processes with senescence and age-associated conditions.
Topics: DNA, Mitochondrial; Humans; Inflammation; Mitochondria; Mitochondrial Membranes
PubMed: 35203322
DOI: 10.3390/cells11040675 -
Trends in Cell Biology Apr 2021Mammalian cells, with the exception of erythrocytes, harbor mitochondria, which are organelles that provide energy, intermediate metabolites, and additional activities... (Review)
Review
Mammalian cells, with the exception of erythrocytes, harbor mitochondria, which are organelles that provide energy, intermediate metabolites, and additional activities to sustain cell viability, replication, and function. Mitochondria contain multiple copies of a circular genome called mitochondrial DNA (mtDNA), whose individual sequences are rarely identical (homoplasmy) because of inherited or sporadic mutations that result in multiple mtDNA genotypes (heteroplasmy). Here, we examine potential mechanisms for maintenance or shifts in heteroplasmy that occur in induced pluripotent stem cells (iPSCs) generated by cellular reprogramming, and further discuss manipulations that can alter heteroplasmy to impact stem and differentiated cell performance. This additional insight will assist in developing more robust iPSC-based models of disease and differentiated cell therapies.
Topics: Animals; Cellular Reprogramming; DNA, Mitochondrial; Induced Pluripotent Stem Cells; Mitochondria; Mitochondrial Dynamics
PubMed: 33422359
DOI: 10.1016/j.tcb.2020.12.009