2004/10/27 by Sara Cipolat, Olga Martins de Brito, Barbara Dal Zilio +1 · 1,271 citations
Biochemistry, Genetics and Molecular Biology · #Mitochondrial Function and Pathology #ATP Synthase and ATPases Research #Metabolism and Genetic Disorders #MFN2 #mitochondrial fusion #MFN1 #Mitochondrion #Cell biology #Mitochondrial fission #Biology #Inner mitochondrial membrane #FIS1 #Biochemistry #Mitochondrial DNA #Gene
paper · pdf · doi:10.1073/pnas.0407043101
published in Proceedings of the National Academy of Sciences 101(45), 15927-15932 (National Academy of Sciences)
openalex publication_date 2004/10/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
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.