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.
- Luke H Chao
- Yifan Ge
- 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.
- Axel T Brunger, Stanford University, United States
- Received: August 9, 2019
- Accepted: January 10, 2020
- Accepted Manuscript published: January 10, 2020 (version 1)
© 2020, Ge et al.
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