ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells
Open accessAbstract
How the ER manages mitochondrial division: It has been unclear how mitochondrial DNA (mtDNA) replication is spatially controlled in mammalian cells and how the mitochondrial nucleoid—the protein-DNA structure that is the unit of mtDNA inheritance—is distributed at the cellular level. Lewis et al. now show that homeostatic mtDNA synthesis in mitochondrial nucleoids in mammalian cells is spatially linked to a small subset of endoplasmic reticulum (ER)-mitochondria contact sites that are specifically destined for mitochondrial division. Successive events of mtDNA replication, mitochondrial division, and mitochondrial motility function together to ensure the accurate distribution of mtDNA in cells. Furthermore, ER-mitochondria contacts coordinate the licensing of mtDNA replication with division to distribute newly replicated nucleoids to daughter mitochondria. Science , this issue p. 261
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Fission occurs at mitochondria-ER contact sites marked with mtDNA.
“Fission occurs at mitochondria–ER contact sites marked with mtDNA [80].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [80]
ERMD increases in the presence of mtDNA, and mtDNA synthesis is coupled to mitochondrial division to ensure distribution of newly replicated mtDNA to daughter mitochondria.
“Importantly, ERMD increases in the presence of mtDNA. Thus, mtDNA synthesis is coupled to mitochondrial division to ensure the distribution of newly replicated mtDNA to daughter mitochondria [80].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [80]
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References 52 · Cited by 673
- Authors
- Lewis, S. C., Uchiyama, L. F., & Nunnari, J.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Nunnari, Jodi
- Venue
- Science
- Published
- 2016-07-15
- Volume
- 353
- Issue
- 6296
- Pages
- aaf5549-aaf5549
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5554545
- OpenAlex
- W2465187827
- Cited by
- 673
- References
- 52
- Citations by year
- 2026: 47 · 2025: 75 · 2024: 73 · 2023: 58 · 2022: 72 · 2021: 79 · 2020: 76 · 2019: 71 · 2018: 59 · 2017: 53 · 2016: 10
- FWCI
- 33.45
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-11-20)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (R01GM106019, R01GM097432)
- NIH Ruth L. Kirschstein Postdoctoral Fellowship (F32GM113388)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- ER-mitochondria contact sites, mitochondrial DNA synthesis, mitochondrial division, replication licensing, mitochondrial distribution, ER tubules, human cells
- MeSH terms
- Animals, Chlorocebus aethiops, DNA-Directed DNA Polymerase, DNA Replication, DNA, Mitochondrial, Endoplasmic Reticulum, Humans, Microscopy, Fluorescence, Mitochondria, Recombinant Proteins, COS Cells, Cell Line, Tumor, Green Fluorescent Proteins, Mitochondrial Dynamics
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