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Clinical Journal of the American... Jul 2022
Topics: DNA, Mitochondrial; Humans; Kidney; Mitochondria
PubMed: 35777832
DOI: 10.2215/CJN.05820522 -
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 -
Sub-cellular Biochemistry 2023Mitochondria are subcellular organelles present in most eukaryotic cells which play a significant role in numerous aspects of cell biology. These include carbohydrate...
Mitochondria are subcellular organelles present in most eukaryotic cells which play a significant role in numerous aspects of cell biology. These include carbohydrate and fatty acid metabolism to generate cellular energy through oxidative phosphorylation, apoptosis, cell signalling, haem biosynthesis and reactive oxygen species production. Mitochondrial dysfunction is a feature of many human ageing tissues, and since the discovery that mitochondrial DNA mutations were a major underlying cause of changes in oxidative phosphorylation capacity, it has been proposed that they have a role in human ageing. However, there is still much debate on whether mitochondrial DNA mutations play a causal role in ageing or are simply a consequence of the ageing process. This chapter describes the structure of mammalian mitochondria, and the unique features of mitochondrial genetics, and reviews the current evidence surrounding the role of mitochondrial DNA mutations in the ageing process. It then focusses on more recent discoveries regarding the role of mitochondrial dysfunction in stem cell ageing and age-related inflammation.
Topics: Animals; Humans; DNA, Mitochondrial; Aging; Mitochondria; Mutation; Reactive Oxygen Species; Oxidative Stress; Mammals
PubMed: 36600130
DOI: 10.1007/978-3-031-21410-3_4 -
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 -
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 -
Current Heart Failure Reports Feb 2023We review pathophysiology and clinical features of mitochondrial disorders manifesting with cardiomyopathy. (Review)
Review
PURPOSE OF REVIEW
We review pathophysiology and clinical features of mitochondrial disorders manifesting with cardiomyopathy.
RECENT FINDINGS
Mechanistic studies have shed light into the underpinnings of mitochondrial disorders, providing novel insights into mitochondrial physiology and identifying new therapeutic targets. Mitochondrial disorders are a group of rare genetic diseases that are caused by mutations in mitochondrial DNA (mtDNA) or in nuclear genes that are essential to mitochondrial function. The clinical picture is extremely heterogeneous, the onset can occur at any age, and virtually, any organ or tissue can be involved. Since the heart relies primarily on mitochondrial oxidative metabolism to fuel contraction and relaxation, cardiac involvement is common in mitochondrial disorders and often represents a major determinant of their prognosis.
Topics: Humans; Heart Failure; Mitochondrial Diseases; DNA, Mitochondrial; Cardiomyopathies; Mutation
PubMed: 36802007
DOI: 10.1007/s11897-023-00592-3 -
Molecular Oncology Sep 2022Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70.... (Review)
Review
Advancing age is a major risk factor for malignant transformation and the development of cancer. As such, over 50% of neoplasms occur in individuals over the age of 70. The pathologies of both ageing and cancer have been characterized by respective groups of molecular hallmarks, and while some features are divergent between the two pathologies, several are shared. Perturbed mitochondrial function is one such common hallmark, and this observation therefore suggests that mitochondrial alterations may be of significance in age-related cancer development. There is now considerable evidence documenting the accumulation of somatic mitochondrial DNA (mtDNA) mutations in ageing human postmitotic and replicative tissues. Similarly, mutations of the mitochondrial genome have been reported in human cancers for decades. The plethora of functions in which mitochondria partake, such as oxidative phosphorylation, redox balance, apoptosis and numerous biosynthetic pathways, manifests a variety of ways in which alterations in mtDNA may contribute to tumour growth. However, the specific mechanisms by which mtDNA mutations contribute to tumour progression remain elusive and often contradictory. This review aims to consolidate current knowledge and describe future direction within the field.
Topics: Aging; DNA, Mitochondrial; Humans; Mitochondria; Mutation; Neoplasms
PubMed: 35842901
DOI: 10.1002/1878-0261.13291 -
Antioxidants & Redox Signaling May 2022The small, multicopy mitochondrial genome (mitochondrial DNA [mtDNA]) is essential for efficient energy production, as alterations in its coding information or a... (Review)
Review
The small, multicopy mitochondrial genome (mitochondrial DNA [mtDNA]) is essential for efficient energy production, as alterations in its coding information or a decrease in its copy number disrupt mitochondrial ATP synthesis. However, the mitochondrial replication machinery encounters numerous challenges that may limit its ability to duplicate this important genome and that jeopardize mtDNA stability, including various lesions in the DNA template, topological stress, and an insufficient nucleotide supply. An ever-growing array of DNA repair or maintenance factors are being reported to localize to the mitochondria. We review current knowledge regarding the mitochondrial factors that may contribute to the tolerance or repair of various types of changes in the mitochondrial genome, such as base damage, incorporated ribonucleotides, and strand breaks. We also discuss the newly discovered link between mtDNA instability and activation of the innate immune response. By which mechanisms do mitochondria respond to challenges that threaten mtDNA maintenance? What types of mtDNA damage are repaired, and when are the affected molecules degraded instead? And, finally, which forms of mtDNA instability trigger an immune response, and how? Further work is required to understand the contribution of the DNA repair and damage-tolerance factors present in the mitochondrial compartment, as well as the balance between mtDNA repair and degradation. Finally, efforts to understand the events underlying mtDNA release into the cytosol are warranted. Pursuing these and many related avenues can improve our understanding of what goes wrong in mitochondrial disease. . 36, 885-905.
Topics: Animals; Cytosol; DNA Damage; DNA Repair; DNA Replication; DNA, Mitochondrial; Mammals; Mitochondria
PubMed: 34015960
DOI: 10.1089/ars.2021.0091 -
BMC Biology Jul 2019Perturbed mitochondrial bioenergetics constitute a core pillar of cancer-associated metabolic dysfunction. While mitochondrial dysfunction in cancer may result... (Review)
Review
Perturbed mitochondrial bioenergetics constitute a core pillar of cancer-associated metabolic dysfunction. While mitochondrial dysfunction in cancer may result from myriad biochemical causes, a historically neglected source is that of the mitochondrial genome. Recent large-scale sequencing efforts and clinical studies have highlighted the prevalence of mutations in mitochondrial DNA (mtDNA) in human tumours and their potential roles in cancer progression. In this review we discuss the biology of the mitochondrial genome, sources of mtDNA mutations, and experimental evidence of a role for mtDNA mutations in cancer. We also propose a 'metabolic licensing' model for mtDNA mutation-derived dysfunction in cancer initiation and progression.
Topics: Animals; Carcinogenesis; DNA, Mitochondrial; Disease Progression; Genome, Mitochondrial; Humans; Mice; Mutation; Neoplasms
PubMed: 31286943
DOI: 10.1186/s12915-019-0668-y -
Cold Spring Harbor Perspectives in... Jul 2019Mitochondria are metabolic hubs that use multiple proteases to maintain proteostasis and to preserve their overall quality. A decline of mitochondrial proteolysis... (Review)
Review
Mitochondria are metabolic hubs that use multiple proteases to maintain proteostasis and to preserve their overall quality. A decline of mitochondrial proteolysis promotes cellular stress and may contribute to the aging process. Mitochondrial proteases have also emerged as tightly regulated enzymes required to support the remarkable mitochondrial plasticity necessary for metabolic adaptation in a number of physiological scenarios. Indeed, the mutation and dysfunction of several mitochondrial proteases can cause specific human diseases with severe metabolic phenotypes. Here, we present an overview of the proteolytic regulation of key mitochondrial functions such as respiration, lipid biosynthesis, and mitochondrial dynamics, all of which are required for metabolic control. We also pay attention to how mitochondrial proteases are acutely regulated in response to cellular stressors or changes in growth conditions, a greater understanding of which may one day uncover their therapeutic potential.
Topics: DNA, Mitochondrial; Gene Expression Regulation, Enzymologic; Genome, Mitochondrial; Peptide Hydrolases; Proteins
PubMed: 30670467
DOI: 10.1101/cshperspect.a033936