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Cells Apr 2019Mitochondrion harbors its own DNA (mtDNA), which encodes many critical proteins for the assembly and activity of mitochondrial respiratory complexes. mtDNA is packed by... (Review)
Review
Mitochondrion harbors its own DNA (mtDNA), which encodes many critical proteins for the assembly and activity of mitochondrial respiratory complexes. mtDNA is packed by many proteins to form a nucleoid that uniformly distributes within the mitochondrial matrix, which is essential for mitochondrial functions. Defects or mutations of mtDNA result in a range of diseases. Damaged mtDNA could be eliminated by mitophagy, and all paternal mtDNA are degraded by endonuclease G or mitophagy during fertilization. In this review, we describe the role and mechanism of mtDNA distribution and elimination. In particular, we focus on the regulation of paternal mtDNA elimination in the process of fertilization.
Topics: DNA, Mitochondrial; Humans; Mitochondria; Mitophagy; Mutation
PubMed: 31027297
DOI: 10.3390/cells8040379 -
Biochimica Et Biophysica Acta.... Jun 2017The maintenance of mitochondrial DNA (mtDNA) depends on a number of nuclear gene-encoded proteins including a battery of enzymes forming the replisome needed to... (Review)
Review
The maintenance of mitochondrial DNA (mtDNA) depends on a number of nuclear gene-encoded proteins including a battery of enzymes forming the replisome needed to synthesize mtDNA. These enzymes need to be in balanced quantities to function properly that is in part achieved by exchanging intramitochondrial contents through mitochondrial fusion. In addition, mtDNA synthesis requires a balanced supply of nucleotides that is achieved by nucleotide recycling inside the mitochondria and import from the cytosol. Mitochondrial DNA maintenance defects (MDMDs) are a group of diseases caused by pathogenic variants in the nuclear genes involved in mtDNA maintenance resulting in impaired mtDNA synthesis leading to quantitative (mtDNA depletion) and qualitative (multiple mtDNA deletions) defects in mtDNA. Defective mtDNA leads to organ dysfunction due to insufficient mtDNA-encoded protein synthesis, resulting in an inadequate energy production to meet the needs of affected organs. MDMDs are inherited as autosomal recessive or dominant traits, and are associated with a broad phenotypic spectrum ranging from mild adult-onset ophthalmoplegia to severe infantile fatal hepatic failure. To date, pathogenic variants in 20 nuclear genes known to be crucial for mtDNA maintenance have been linked to MDMDs, including genes encoding enzymes of mtDNA replication machinery (POLG, POLG2, TWNK, TFAM, RNASEH1, MGME1, and DNA2), genes encoding proteins that function in maintaining a balanced mitochondrial nucleotide pool (TK2, DGUOK, SUCLG1, SUCLA2, ABAT, RRM2B, TYMP, SLC25A4, AGK, and MPV17), and genes encoding proteins involved in mitochondrial fusion (OPA1, MFN2, and FBXL4).
Topics: Animals; DNA Damage; DNA, Mitochondrial; Humans; Mitochondrial Diseases; Mitochondrial Proteins
PubMed: 28215579
DOI: 10.1016/j.bbadis.2017.02.017 -
Cells Jan 2019As 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... (Review)
Review
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.
Topics: DNA Damage; DNA Replication; DNA, Mitochondrial; Disease; Health; Humans; Transcription, Genetic
PubMed: 30700008
DOI: 10.3390/cells8020100 -
The Journal of Biological Chemistry Dec 2020Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and... (Review)
Review
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 re-constituted transcriptional complexes of (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.
Topics: DNA, Mitochondrial; Gene Expression Regulation; Humans; Mitochondrial Proteins; Transcription Factors; Transcription Initiation Site; Transcription, Genetic
PubMed: 33127643
DOI: 10.1074/jbc.REV120.011202 -
FEBS Letters Jul 2019The incorporation of ribonucleotides (rNMPs) into DNA during genome replication has gained substantial attention in recent years and has been shown to be a significant... (Review)
Review
The incorporation of ribonucleotides (rNMPs) into DNA during genome replication has gained substantial attention in recent years and has been shown to be a significant source of genomic instability. Studies in yeast and mammals have shown that the two genomes, the nuclear DNA (nDNA) and the mitochondrial DNA (mtDNA), differ with regard to their rNMP content. This is largely due to differences in rNMP repair - whereas rNMPs are efficiently removed from the nuclear genome, mitochondria lack robust mechanisms for removal of single rNMPs incorporated during DNA replication. In this minireview, we describe the processes that determine the frequency of rNMPs in the mitochondrial genome and summarise recent findings regarding the effect of incorporated rNMPs on mtDNA stability and function.
Topics: Animals; Cell Nucleus; DNA, Mitochondrial; Humans; Ribonucleotides
PubMed: 31093968
DOI: 10.1002/1873-3468.13440 -
Clinical Journal of the American... Jul 2022
Topics: DNA, Mitochondrial; Humans; Kidney; Mitochondria
PubMed: 35777832
DOI: 10.2215/CJN.05820522 -
Mitochondrial DNA. Part A, DNA Mapping,... Mar 2020
Topics: DNA Barcoding, Taxonomic; DNA, Mitochondrial; Genome, Mitochondrial; Humans; Phylogeny; Reactive Oxygen Species
PubMed: 32148154
DOI: 10.1080/24701394.2020.1734586 -
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 -
Methods in Molecular Biology (Clifton,... 2023Mitochondrial DNA (mtDNA) is a 16,569 base pair (bp) circular genome that is passed from generation to generation through the maternal line. mtDNA analysis in the...
Mitochondrial DNA (mtDNA) is a 16,569 base pair (bp) circular genome that is passed from generation to generation through the maternal line. mtDNA analysis in the context of the forensic science field usually involves unidentified human remains or missing persons. These cases tend to have more challenging sample types (e.g., rootless hairs, bone, blood, and saliva), and mtDNA analysis can be an additional method to assist in identification efforts. Due to the multifaceted protection of mtDNA within cells, mtDNA is able to be extracted even in cases of extreme degradation. mtDNA analysis for forensic science has been both peer-reviewed in academic journals and has been testified to in criminal court procedures since the late 1990s, allowing for consistent and reliable usage in casework. This chapter describes the general methodology of extracting, amplifying, quantifying, and analyzing an mtDNA sequence for use in forensic casework, specifically for these common items of evidence.
Topics: Humans; DNA, Mitochondrial; DNA Fingerprinting; Sequence Analysis, DNA; Hair; Bone and Bones; Forensic Genetics
PubMed: 37439991
DOI: 10.1007/978-1-0716-3295-6_20 -
Chemical Research in Toxicology Oct 2020Mitochondria have a plethora of functions within a eukaryotic cell, ranging from energy production, cell signaling, and protein cofactor synthesis to various aspects of... (Review)
Review
Mitochondria have a plethora of functions within a eukaryotic cell, ranging from energy production, cell signaling, and protein cofactor synthesis to various aspects of metabolism. Mitochondrial dysfunction is known to cause over 200 named disorders and has been implicated in many human diseases and aging. Mitochondria have their own genetic material, mitochondrial DNA (mtDNA), which encodes 13 protein subunits in the oxidative phosphorylation system and a full set of transfer and rRNAs. Although more than 99% of the proteins in mitochondria are nuclear DNA (nDNA)-encoded, the integrity of mtDNA is critical for mitochondrial functions, as evidenced by mitochondrial diseases sourced from mtDNA mutations and depletions and the vital role of fragmented mtDNA molecules in cell signaling pathways. Previous research has shown that mtDNA is an important target of genotoxic assaults by a variety of chemical and physical factors. This Perspective discusses the prevalence of mtDNA damage by comparing the abundance of lesions in mDNA and nDNA and summarizes current knowledge on the biological pathways to cope with mtDNA damage, including mtDNA repair, mtDNA degradation, and mitochondrial fission and fusion. Also, emerging roles of mtDNA damage in mutagenesis and immune responses are reviewed.
Topics: Animals; DNA Damage; DNA, Mitochondrial; Humans
PubMed: 32486637
DOI: 10.1021/acs.chemrestox.0c00083