ArticleScientific reports2015
Human Mitochondrial DNA-Protein Complexes Attach to a Cholesterol-Rich Membrane Structure.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers.
What it found
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Who cites it
60 citing papers in PubMed, 101 citations in OpenAlex.
- ATAD3 megadalton complex in Plasmodium falciparum is essential for mitochondrial and cellular viability.PLoS pathogens · 2026Article
- Cholesterol in Mitochondrial Diseases-Friend or Foe?International journal of molecular sciences · 2026Review
- Mitochondrial DNA replication is regulated by endoplasmic reticulum-mitochondrial contact sites, the mitochondrial calcium uniporter, and manganese.Nucleic acids research · 2026Article
- The segregation of organelles and organellar genomes across eukaryotic biology.Biochemical Society transactions · 2026Review
- Transcriptome analysis of atad3-null zebrafish embryos elucidates possible disease mechanisms.Orphanet journal of rare diseases · 2025Article
- Transcriptional Regulation Mechanisms in Adaptively EvolvedJournal of fungi (Basel, Switzerland) · 2025Article
- Molecular mechanisms of mitochondrial dynamics.Nature reviews. Molecular cell biology · 2025Review
- Elevated cholesterol in ATAD3 mutants is a compensatory mechanism that leads to membrane cholesterol aggregation.Brain : a journal of neurology · 2024Article
- Decoding the nature and complexity of extracellular mtDNA: Types and implications for health and disease.Mitochondrion · 2024Article
- Decoding the mitochondria without a code: mechanistic insights into mitochondrial DNA depletion syndromes.Journal of biosciences · 2024Review
- Mutations in mitochondrialFrontiers in neuroscience · 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
- Mitochondrial DNA Release in Innate Immune Signaling.Annual review of biochemistry · 2023Review
- Altered Lysosomal Function Manipulates Cellular Biosynthetic Capacity By Remodeling Intracellular Cholesterol Distribution.Cell biochemistry and biophysics · 2023Article
- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- Mitochondrial nucleoid trafficking regulated by the inner-membrane AAA-ATPase ATAD3A modulates respiratory complex formation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Allylamines, Benzylamines, and Fungal Cell Permeability: A Review of Mechanistic Effects and Usefulness against Fungal Pathogens.Membranes · 2022Review
- Fundamental roles for inter-organelle communication in aging.Biochemical Society transactions · 2022Review
- Method for the structural analysis of Twinkle mitochondrial DNA helicase by cryo-EM.Methods (San Diego, Calif.) · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
Abstract
The helicase Twinkle is indispensable for mtDNA replication in nucleoids. Previously, we showed that Twinkle is tightly membrane-associated even in the absence of mtDNA, which suggests that Twinkle is part of a membrane-attached replication platform. Here we show that this platform is a cholesterol-rich membrane structure. We fractionated mitochondrial membrane preparations on flotation gradients and show that membrane-associated nucleoids accumulate at the top of the gradient. This fraction was shown to be highly enriched in cholesterol, a lipid that is otherwise low abundant in mitochondria. In contrast, more common mitochondrial lipids, and abundant inner-membrane associated proteins concentrated in the bottom-half of these gradients. Gene silencing of ATAD3, a protein with proposed functions related to nucleoid and mitochondrial cholesterol homeostasis, modified the distribution of cholesterol and nucleoids in the gradient in an identical fashion. Both cholesterol and ATAD3 were previously shown to be enriched in ER-mitochondrial junctions, and we detect nucleoid components in biochemical isolates of these structures. Our data suggest an uncommon membrane composition that accommodates platforms for replicating mtDNA, and reconcile apparently disparate functions of ATAD3. We suggest that mtDNA replication platforms are organized in connection with ER-mitochondrial junctions, facilitated by a specialized membrane architecture involving mitochondrial cholesterol.
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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.