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Frontiers in Bioscience (Landmark... Jan 2017Plants possess mitochondrial genomes that are large and complex compared to animals. Nearly all animal mitochondrial genomes are about 16.5. kbp in length, whereas plant... (Review)
Review
Plants possess mitochondrial genomes that are large and complex compared to animals. Nearly all animal mitochondrial genomes are about 16.5. kbp in length, whereas plant mitochondrial genomes range between 200-2,000 kbp. This is curious if we assume modern mitochondria originated from a common alpha-proteobacterial ancestor. Despite their size, plant mitochondrial genomes do not contain significantly more genes than their animal counterparts. Most of the additional DNA found in plant mitochondrial genomes consists of large introns, repeats and non-coding regions. Furthermore, plant mtDNA does not exist as large circular DNA molecules but mostly as a collection of linear DNA with combinations of smaller circular and branched molecules. Studies into these highly fragmented genomes heavily imply that recombination is the main mechanism driving replication of plant mtDNA.
Topics: DNA Replication; DNA, Mitochondrial; DNA, Plant; Genome, Mitochondrial; Genome, Plant; Mitochondria; Phylogeny
PubMed: 27814661
DOI: 10.2741/4531 -
Cells Oct 2023Mitochondria are subcontractors dedicated to energy production within cells. In human mitochondria, almost all mitochondrial proteins originate from the nucleus, except... (Review)
Review
Mitochondria are subcontractors dedicated to energy production within cells. In human mitochondria, almost all mitochondrial proteins originate from the nucleus, except for 13 subunit proteins that make up the crucial system required to perform 'oxidative phosphorylation (OX PHOS)', which are expressed by the mitochondria's self-contained DNA. Mitochondrial DNA (mtDNA) also encodes 2 rRNA and 22 tRNA species. Mitochondrial DNA replicates almost autonomously, independent of the nucleus, and its heredity follows a non-Mendelian pattern, exclusively passing from mother to children. Numerous studies have identified mtDNA mutation-related genetic diseases. The consequences of various types of mtDNA mutations, including insertions, deletions, and single base-pair mutations, are studied to reveal their relationship to mitochondrial diseases. Most mitochondrial diseases exhibit fatal symptoms, leading to ongoing therapeutic research with diverse approaches such as stimulating the defective OXPHOS system, mitochondrial replacement, and allotropic expression of defective enzymes. This review provides detailed information on two topics: (1) mitochondrial diseases caused by mtDNA mutations, and (2) the mechanisms of current treatments for mitochondrial diseases and clinical trials.
Topics: Child; Humans; Mitochondrial Diseases; Mitochondria; DNA, Mitochondrial; Oxidative Phosphorylation; Mutation
PubMed: 37887337
DOI: 10.3390/cells12202494 -
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 -
Physiology (Bethesda, Md.) Jul 2022Circulating cell-free mitochondrial DNA (ccf-mtDNA) released upon cell injury or death stimulates diverse pattern recognition receptors to activate innate immune... (Review)
Review
Circulating cell-free mitochondrial DNA (ccf-mtDNA) released upon cell injury or death stimulates diverse pattern recognition receptors to activate innate immune responses and initiate systemic inflammation. In this review, we discuss the temporal changes of ccf-mtDNA during pregnancy and its potential contribution to adverse pregnancy outcomes in pregnancy complications.
Topics: Cell-Free Nucleic Acids; DNA, Mitochondrial; Female; Humans; Inflammation; Mitochondria; Pregnancy
PubMed: 35001655
DOI: 10.1152/physiol.00037.2021 -
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 -
FEMS Microbiology Reviews Nov 2023Mitochondrial DNA replication is an essential process in most eukaryotes. Similar to the diversity in mitochondrial genome size and organization in the different... (Review)
Review
Mitochondrial DNA replication is an essential process in most eukaryotes. Similar to the diversity in mitochondrial genome size and organization in the different eukaryotic supergroups, there is considerable diversity in the replication process of the mitochondrial DNA. In this review, we summarize the current knowledge of mitochondrial DNA replication and the associated factors in trypanosomes with a focus on Trypanosoma brucei, and provide a new model of minicircle replication for this protozoan parasite. The model assumes the mitochondrial DNA (kinetoplast DNA, kDNA) of T. brucei to be loosely diploid in nature and the replication of the genome to occur at two replication centers at the opposing ends of the kDNA disc (also known as antipodal sites, APS). The new model is consistent with the localization of most replication factors and in contrast to the current model, it does not require the assumption of an unknown sorting and transport complex moving freshly replicated DNA to the APS. In combination with the previously proposed sexual stages of the parasite in the insect vector, the new model provides a mechanism for maintenance of the mitochondrial genetic diversity.
Topics: DNA, Kinetoplast; Genome, Mitochondrial; DNA Replication; DNA, Mitochondrial; Mitochondria; Protozoan Proteins
PubMed: 36449697
DOI: 10.1093/femsre/fuac047 -
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 -
International Journal of Molecular... May 2023In human spermatozoa and oocytes (and their surrounding granulosa cells), mitochondria carry out important functions relating to human fertility and infertility. Sperm...
In human spermatozoa and oocytes (and their surrounding granulosa cells), mitochondria carry out important functions relating to human fertility and infertility. Sperm mitochondria are not transmitted to the future embryo, but are closely related to the generation of energy needed for sperm movement, capacitation, and acrosome reactions, as well as for sperm-oocyte fusion. On the other hand, oocyte mitochondria produce energy required for oocyte meiotic division and their abnormalities can thus cause oocyte and embryo aneuploidy. In addition, they play a role in oocyte calcium metabolism and in essential epigenetic events during the oocyte-to-embryo transition. They are transmitted to the future embryos and may thus cause hereditary diseases in the offspring. Due to the long life span of the female germ cells, the accumulation of mitochondrial DNA abnormalities often causes ovarian aging. Mitochondrial substitution therapy is the only way of dealing with these issues nowadays. New therapies based on mitochondrial DNA editing are under investigation.
Topics: Humans; Male; Female; Semen; Infertility; Mitochondria; DNA, Mitochondrial; Oocytes; Fertility
PubMed: 37240296
DOI: 10.3390/ijms24108950 -
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