RT Journal Article
SR Electronic
T1 Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 739078
DO 10.1101/739078
A1 Yifan Ge
A1 Xiaojun Shi
A1 Sivakumar Boopathy
A1 Julie McDonald
A1 Adam W. Smith
A1 Luke H. Chao
YR 2019
UL http://biorxiv.org/content/early/2019/08/18/739078.abstract
AB Mitochondrial membrane dynamics is a cellular rheostat that relates organelle morphology and metabolic function. 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 in conditions of abnormal cellular proteostasis. These observations describe a mechanism for gating membrane fusion.