Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
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.
Data availability
All data generated or analyses during this study are include in the manuscript and supporting files.
Article and author information
Author details
Funding
Charles H Hood Foundation (Child Health Research Award)
- Luke H Chao
Charles H Hood Foundation (Child Health Research Award)
- Yifan Ge
National Science Foundation (CHE-1753060)
- Xiaojun Shi
- Adam W Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Axel T Brunger, Stanford University, United States
Version history
- Received: August 9, 2019
- Accepted: January 10, 2020
- Accepted Manuscript published: January 10, 2020 (version 1)
- Version of Record published: January 24, 2020 (version 2)
Copyright
© 2020, Ge et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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