ArticleNucleic acids research2014
Replication factors transiently associate with mtDNA at the mitochondrial inner membrane to facilitate replication.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 81 citations in OpenAlex.
- Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial.Orphanet journal of rare diseases · 2024Trial
- Retrograde mitochondrial transport is required for mitochondrial biogenesis in zebrafish neurons.Nature communications · 2026Article
- Mitochondrial DNA replication is regulated by endoplasmic reticulum-mitochondrial contact sites, the mitochondrial calcium uniporter, and manganese.Nucleic acids research · 2026Article
- Mitochondria and the epigenome: maternal co-inheritance and crosstalk from oocyte to embryo.Cell communication and signaling : CCS · 2026Review
- Retrograde mitochondrial transport regulates mitochondrial biogenesis in zebrafish neurons.bioRxiv : the preprint server for biology · 2025Article
- ALS-Linked VapB P56S Mutation Alters Neuronal Mitochondrial Turnover at the Synapse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- TOP3A coupling with replication forks and repair of TOP3A cleavage complexes.Cell cycle (Georgetown, Tex.) · 2024Review
- RCCD1 promotes breast carcinogenesis through regulating hypoxia-associated mitochondrial homeostasis.Oncogene · 2023Article
- Uncharacterized protein C17orf80 - a novel interactor of human mitochondrial nucleoids.Journal of cell science · 2023Article
- Article
- Two type I topoisomerases maintain DNA topology in human mitochondria.Nucleic acids research · 2022Article
- Article
- Mitochondrial DNA mutations in ageing and cancer.Molecular oncology · 2022Review
- Method for the structural analysis of Twinkle mitochondrial DNA helicase by cryo-EM.Methods (San Diego, Calif.) · 2022Article
- Most mitochondrial dGTP is tightly bound to respiratory complex I through the NDUFA10 subunit.Communications biology · 2022Article
- Mitochondrial Membranes and Mitochondrial Genome: Interactions and Clinical Syndromes.Membranes · 2022Review
- TFAM knockdown-triggered mtDNA-nucleoid aggregation and a decrease in mtDNA copy number induce the reorganization of nucleoid populations and mitochondria-associated ER-membrane contacts.Biochemistry and biophysics reports · 2021Article
- RNA Granules in the Mitochondria and Their Organization under Mitochondrial Stresses.International journal of molecular sciences · 2021Review
- Controlling the topology of mammalian mitochondrial DNA.Open biology · 2021Review
- Implications of Membrane Binding by the Fe-S Cluster-Containing N-Terminal Domain in theFrontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial DNA (mtDNA) is organized in discrete protein-DNA complexes, nucleoids, that are usually considered to be mitochondrial-inner-membrane associated. Here we addressed the association of replication factors with nucleoids and show that endogenous mtDNA helicase Twinkle and single-stranded DNA-binding protein, mtSSB, co-localize only with a subset of nucleoids. Using nucleotide analogs to identify replicating mtDNA in situ, the fraction of label-positive nucleoids that is Twinkle/mtSSB positive, is highest with the shortest labeling-pulse. In addition, the recruitment of mtSSB is shown to be Twinkle dependent. These proteins thus transiently associate with mtDNA in an ordered manner to facilitate replication. To understand the nature of mtDNA replication complexes, we examined nucleoid protein membrane association and show that endogenous Twinkle is firmly membrane associated even in the absence of mtDNA, whereas mtSSB and other nucleoid-associated proteins are found in both membrane-bound and soluble fractions. Likewise, a substantial amount of mtDNA is found as soluble or loosely membrane bound. We show that, by manipulation of Twinkle levels, mtDNA membrane association is partially dependent on Twinkle. Our results thus show that Twinkle recruits or is assembled with mtDNA at the inner membrane to form a replication platform and amount to the first clear demonstration that nucleoids are dynamic both in composition and concurrent activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.