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Cited by 174Mitochondrial Function and PathologyAutophagy in Disease and TherapyATP Synthase and ATPases Research

Two Forms of Opa1 Cooperate to Complete Fusion of the Mitochondrial Inner-Membrane

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Ge, Yifan, Shi, Xiaojun, Boopathy, Sivakumar, McDonald, Julie, Smith, Adam W, Chao, Luke H·2020·eLife
DOI 10.7554/elife.50973PMC PMC7299343

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Abstract

Mitochondrial membrane dynamics is a cellular rheostat that relates metabolic function and organelle morphology. Using an in vitro reconstitution system, we describe a mechanism for how mitochondrial inner-membrane fusion is regulated by the ratio of two forms of Opa1. We found that the long-form of Opa1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release. However, stoichiometric levels of the processed, short form of Opa1 (s-Opa1) work together with l-Opa1 to mediate efficient and fast membrane pore opening. Additionally, we found that excess levels of s-Opa1 inhibit fusion activity, as seen under conditions of altered proteostasis. These observations describe a mechanism for gating membrane fusion.

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Cited by

Sorted by citations

Authors
Ge, Y., Shi, X., Boopathy, S., McDonald, J., Smith, A. W., & Chao, L. H.
Affiliations
  • Harvard University (US)
  • University of Akron (US)
Corresponding author
Chao, Luke H
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2020-01-10
Volume
9
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.50973
PMC
PMC7299343
OpenAlex
W2999878740
Cited by
174
References
4
Citations by year
2026: 22 · 2025: 28 · 2024: 26 · 2023: 35 · 2022: 25 · 2021: 22 · 2020: 16
FWCI
7.85
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Charles H. Hood Foundation (Child Health Research Award)
  • National Science Foundation (CHE-1753060)
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
OPA1, hemifusion, membrane docking, proteostasis, in vitro reconstitution
MeSH terms
Guanosine Triphosphate, Humans, Lipid Bilayers, Membrane Fusion, Mitochondria, GTP Phosphohydrolases, Mitochondrial Proteins, Mitochondrial Membranes, Mitochondrial Dynamics

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