OPA1 requires mitofusin 1 to promote mitochondrial fusion.
The regulated equilibrium between mitochondrial fusion and fission is essential to maintain integrity of the organelle. Mechanisms of mitochondrial fusion are largely uncharacterized in mammalian cells. It is unclear whether OPA1, a dynamin-related protein of the inner membrane mutated in autosomal dominant optic atrophy, participates in fusion or fission. OPA1 promoted the formation of a branched network of elongated mitochondria, requiring the integrity of both its GTPase and C-terminal coiled-coil domain. Stable reduction of OPA1 levels by RNA interference resulted in small, fragmented, and scattered mitochondria. Levels of OPA1 did not affect mitochondrial docking, but they correlated with the extent of fusion as measured by polyethylene glycol mitochondrial fusion assays. A genetic analysis proved that OPA1 was unable to tubulate and fuse mitochondria lacking the outer membrane mitofusin 1 but not mitofusin 2. Our data show that OPA1 functionally requires mitofusin 1 to regulate mitochondrial fusion and reveal a specific functional difference between mitofusin 1 and 2.
Cipolat
Sara
S
Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, I-35129 Padua, Italy.
Martins de Brito
Olga
O
Dal Zilio
Barbara
B
Scorrano
Luca
L
D000818:Animals; D002478:Cells, Cultured; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D066298:In Vitro Techniques; D008561:Membrane Fusion; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D034622:RNA Interference
D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse; C498809:Opa1 protein, mouse