Fusion

mitochondrial fusion

Organelle

Fusion mechanism

Mitochondrial DNA

Membrane

Inner mitochondrial membrane

Biology

Gene

Lipid bilayer fusion

Biophysics

Translocase of the inner membrane

Philosophy

Chemistry

Linguistics

Proteostasis

Mitochondrion

Cell biology

Biochemistry

Inner membrane

Mitochondrial membrane transport protein

Translocase of the outer membrane

ATP–ADP translocase

eLife

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.

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