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Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane.

Yifan GeXiaojun ShiSivakumar BoopathyJulie L McDonaldAdam W SmithLuke H Chao
Published in: eLife (2020)
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.
Keyphrases
  • oxidative stress
  • molecular dynamics
  • small molecule