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Cited by 52Mitochondrial Function and PathologyATP Synthase and ATPases ResearchAutophagy in Disease and Therapy

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Structural basis for regulated assembly of the mitochondrial fission GTPase Drp1

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Rochon, Kristy, Bauer, Brianna L., Roethler, Nathaniel A., Buckley, Yuli, Su, Chih-Chia, Huang, Wei, Ramachandran, Rajesh, Stoll, Maria S. K., Yu, Edward W., Taylor, Derek J., Mears, Jason A.·2024·Nature Communications
DOI 10.1038/s41467-024-45524-4PMC PMC10864337

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Abstract

Mitochondrial fission is a critical cellular event to maintain organelle function. This multistep process is initiated by the enhanced recruitment and oligomerization of dynamin-related protein 1 (Drp1) at the surface of mitochondria. As such, Drp1 is essential for inducing mitochondrial division in mammalian cells, and homologous proteins are found in all eukaryotes. As a member of the dynamin superfamily of proteins (DSPs), controlled Drp1 self-assembly into large helical polymers stimulates its GTPase activity to promote membrane constriction. Still, little is known about the mechanisms that regulate correct spatial and temporal assembly of the fission machinery. Here we present a cryo-EM structure of a full-length Drp1 dimer in an auto-inhibited state. This dimer reveals two key conformational rearrangements that must be unlocked through intramolecular rearrangements to achieve the assembly-competent state observed in previous structures. This structural insight provides understanding into the mechanism for regulated self-assembly of the mitochondrial fission machinery.

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References 40 · Cited by 52

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Metadata

Authors
Rochon, K., Bauer, B. L., Roethler, N. A., Buckley, Y., Su, C.-C., Huang, W., Ramachandran, R., Stoll, M. S. K., Yu, E. W., Taylor, D. J., & Mears, J. A.
Affiliations
Case Western Reserve University (US)
Corresponding author
Mears, Jason A.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-02-13
Volume
15
Issue
1
Pages
1328-1328
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-45524-4
PMC
PMC10864337
OpenAlex
W4391786421
Cited by
52
References
40
Citations by year
2026: 24 · 2025: 22 · 2024: 5
FWCI
6.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R01 GM125844, F31 GM139324, U24 GM116792)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
Drp1, mitochondrial fission, dynamin-related proteins, dynamin superfamily, GTPase activity, protein self-assembly, conformational change, mitochondrial division, membrane constriction
MeSH terms
Animals, Mammals, Microtubule-Associated Proteins, Mitochondria, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, Mitochondrial Dynamics

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