Unique features of DNA replication in mitochondria: A functional and evolutionary perspective

Holt, Ian; Jacobs, Howard T.

doi:10.1002/bies.201400052

Cited by 33 publications

(29 citation statements)

References 74 publications

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“…A weakness of this so-called bootlace model is that the enzymes required for the process-that is, the hybridization of RNA intermediates to DNA and the subsequent RNA displacement-have not been defined (122). Furthermore, it is unclear how well highly structured and modified tRNAs and rRNAs can be melted to anneal to ssDNA (122). Another strong argument against the RITOLS model is that the in vivo occupancy profile of mtSSB is in good agreement with the SDM (111).…”

Section: Figurementioning

confidence: 92%

“…Both of these models are primarily based on mtDNA replication intermediates observed using neutral two-dimensional agarose gel electrophoresis (known as 2D-AGE). The generality of the strand-coupled DNA replication mechanism has been questioned because products interpreted as intermediates from this type of replication mechanism do not become rapidly labeled in organello (121,122). The RITOLS replication model and the SDM are similar, with the exception of the requirement for mtSSB.…”

Section: Figurementioning

confidence: 94%

“…The RNA intermediates in the RITOLS model are processed transcripts (including tRNAs and rRNAs), which are successively threaded onto the lagging-strand template as the replication fork advances, and they remain hybridized until displaced, degraded, or processed further during lagging-strand DNA synthesis (121). A weakness of this so-called bootlace model is that the enzymes required for the process-that is, the hybridization of RNA intermediates to DNA and the subsequent RNA displacement-have not been defined (122). Furthermore, it is unclear how well highly structured and modified tRNAs and rRNAs can be melted to anneal to ssDNA (122).…”

Section: Figurementioning

confidence: 99%

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Maintenance and Expression of Mammalian Mitochondrial DNA

Gustafsson

Falkenberg

Larsson

2016

Annu. Rev. Biochem.

587

509

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Mammalian mitochondrial DNA (mtDNA) encodes 13 proteins that are essential for the function of the oxidative phosphorylation system, which is composed of four respiratory-chain complexes and adenosine triphosphate (ATP) synthase. Remarkably, the maintenance and expression of mtDNA depend on the mitochondrial import of hundreds of nuclear-encoded proteins that control genome maintenance, replication, transcription, RNA maturation, and mitochondrial translation. The importance of this complex regulatory system is underscored by the identification of numerous mutations of nuclear genes that impair mtDNA maintenance and expression at different levels, causing human mitochondrial diseases with pleiotropic clinical manifestations. The basic scientific understanding of the mechanisms controlling mtDNA function has progressed considerably during the past few years, thanks to advances in biochemistry, genetics, and structural biology. The challenges for the future will be to understand how mtDNA maintenance and expression are regulated and to what extent direct intramitochondrial cross talk between different processes, such as transcription and translation, is important.

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Section: Figurementioning

confidence: 92%

Section: Figurementioning

confidence: 94%

Section: Figurementioning

confidence: 99%

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Maintenance and Expression of Mammalian Mitochondrial DNA

Gustafsson

Falkenberg

Larsson

2016

Annu. Rev. Biochem.

587

509

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“…There are two leading theories to explain the mode of mtDNA replication in animals: an asynchronous strand displacement model and a strand-coupled bidirectional replication model [3, 4]. More recently, other methods of replication have been proposed, including bootlace and rolling circle models [5, 6]. By investigating cases of unusual metazoan mtDNA structure, we may gain insight into the maintenance of normal mtDNA and factors leading to disease associated abnormalities.…”

Section: Introductionmentioning

confidence: 99%

The mitochondrial genome of Globodera ellingtonae is composed of two circles with segregated gene content and differential copy numbers

et al. 2016

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BackgroundThe evolution of animal mitochondrial (mt) genomes has resulted in a highly conserved structure: a single compact circular chromosome approximately 14 to 20 kb long. Within the last two decades exceptions to this conserved structure, such as the division of the genome into multiple chromosomes, have been reported in a diverse set of metazoans. We report on the two circle multipartite mt genome of a newly described cyst nematode, Globodera ellingtonae.ResultsThe G. ellingtonae mt genome was found to be comprised of two circles, each larger than any other multipartite circular mt chromosome yet reported, and both were larger than the single mt circle of the model nematode Caenorhabditis elegans. The genetic content of the genome was disproportionately divided between the two circles, although they shared a ~6.5 kb non-coding region. The 17.8 kb circle (mtDNA-I) contained ten protein-coding genes and two tRNA genes, whereas the 14.4 kb circle (mtDNA-II) contained two protein-coding genes, 20 tRNA genes and both rRNA genes. Perhaps correlated with this division of genetic content, the copy number of mtDNA-II was more than four-fold that of mtDNA-I in individual nematodes. The difference in copy number increased between second-stage and fourth-stage juveniles.ConclusionsThe segregation of gene types to different mt circles in G. ellingtonae could provide benefit by localizing gene functional types to independent transcriptional units. This is the first report of both two-circle and several-circle mt genomes within a single genus. The differential copy number associated with this multipartite mt organization could provide a model system for deconstructing mechanisms regulating mtDNA copy number both in somatic cells and during germline development.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3047-x) contains supplementary material, which is available to authorized users.

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“…Furthermore, mitochondrial genomes replicate in a manner that is radically different from the mammalian DNA replication mechanisms, utilizing the “bootstrap” method in which processed transcripts (bootlaces) hybridize with the displaced parental strand as the replication fork advances [68]. This mechanism minimizes the occurrence and impact of single-strand breaks that threaten genome stability, limit the occurrence of replication-dependent deletions and insertions, and defend against invading elements such as viruses.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial quality control: Easy come, easy go

Stotland¹,

Gottlieb²

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“Friends come and go but enemies accumulate.”Arthur Bloch Mitochondrial networks in eukaryotic cells are maintained via regular cycles of degradation and biogenesis. These complex processes function in concert with one another to eliminate dysfunctional mitochondria in a specific and targeted manner and coordinate the biogenesis of new organelles. This review covers the two aspects of mitochondrial turnover, focusing on the main pathways and mechanisms involved. The review also summarizes the current methods and techniques for analyzing mitochondrial turnover in vivo and in vitro, from the whole animal proteome level to the level of single organelle.

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Unique features of DNA replication in mitochondria: A functional and evolutionary perspective

Cited by 33 publications

References 74 publications

Maintenance and Expression of Mammalian Mitochondrial DNA

Maintenance and Expression of Mammalian Mitochondrial DNA

The mitochondrial genome of Globodera ellingtonae is composed of two circles with segregated gene content and differential copy numbers

Mitochondrial quality control: Easy come, easy go

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