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.
© 2020, Ge et al.
Conflict of interest statement
YG, XS, SB, JM, AS, LC No competing interests declared
Molecular Basis of Selective Mitochondrial Fusion by Heterotypic Action Between OPA1 and CardiolipinT Ban et al. Nat Cell Biol 19 (7), 856-863. PMID 28628083.Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. Optic atrophy 1 (OPA1) is an essential GTPase protein for both mitochondrial inner me …
Relationship Between OPA1 and Cardiolipin in Mitochondrial Inner-Membrane FusionT Ban et al. Biochim Biophys Acta Bioenerg 1859 (9), 951-957. PMID 29852142.Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. The large GTPase optic atrophy 1 (OPA1) is identified as a core component of inner me …
The Short Variant of the Mitochondrial Dynamin OPA1 Maintains Mitochondrial Energetics and Cristae StructureH Lee et al. J Biol Chem 292 (17), 7115-7130. PMID 28298442.The protein optic atrophy 1 (OPA1) is a dynamin-related protein associated with the inner mitochondrial membrane and functions in mitochondrial inner membrane fusion and …
OPA1 Processing in Cell Death and Disease - The Long and Short of ItT MacVicar et al. J Cell Sci 129 (12), 2297-306. PMID 27189080. - ReviewThe regulation of mitochondrial dynamics by the GTPase OPA1, which is located at the inner mitochondrial membrane, is crucial for adapting mitochondrial function and pres …
A Cut Short to Death: Parl and Opa1 in the Regulation of Mitochondrial Morphology and ApoptosisL Pellegrini et al. Cell Death Differ 14 (7), 1275-84. PMID 17464328. - ReviewMitochondria are crucial amplifiers of death signals. They release cytochrome c and other pro-apoptotic factors required to fully activate effector caspases. This release …