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

Elife. 2020 Jan 10;9:e50973. doi: 10.7554/eLife.50973.

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.

Keywords: fusion; in vitro reconstitution; membranes; mitochondria; molecular biophysics; none; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • Guanosine Triphosphate / metabolism
  • Humans
  • Lipid Bilayers
  • Membrane Fusion
  • Mitochondria / physiology*
  • Mitochondrial Dynamics*
  • Mitochondrial Membranes / physiology*
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proteins / chemistry
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism

Substances

  • Lipid Bilayers
  • Mitochondrial Proteins
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • OPA1 protein, human