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PMID: 15509649 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

OPA1 requires mitofusin 1 to promote mitochondrial fusion.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 45 ·2004-11-09 ·Pages 15927-32

Cipolat S, Martins de Brito O, Dal Zilio B, Scorrano L

Abstract

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.

MeSH Terms
Animals Cells, Cultured GTP Phosphohydrolases/antagonists & inhibitors,deficiency,genetics,physiology Gene Targeting In Vitro Techniques Membrane Fusion Mice Mice, Knockout Mitochondria/physiology,ultrastructure RNA Interference
Chemicals
GTP Phosphohydrolases Mfn1 protein, mouse Mfn2 protein, mouse Opa1 protein, mouse
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cipolat Sara
Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, I-35129 Padua, Italy.
Martins de Brito Olga
Dal Zilio Barbara
Scorrano Luca
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0407043101
Published
2004-11-09
Epub
2004-00-27
Pages
15927-32
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC528769
Subset
IM
Grants
Telethon · TCP02016 · Italy
External Links
PubMed source DOI: 10.1073/pnas.0407043101 PMC Full Text View journal details
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