A Caltech Library Service

OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L

Song, Zhiyin and Chen, Hsiuchen and Fiket, Maja and Alexander, Christiane and Chan, David C. (2007) OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. Journal of Cell Biology, 178 (5). pp. 749-755. ISSN 0021-9525. PMCID PMC2064540.

PDF - Published Version
See Usage Policy.

Image (JPEG) (Supplementary Figure S1) - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


OPA1, a dynamin-related guanosine triphosphatase mutated in dominant optic atrophy, is required for the fusion of mitochondria. Proteolytic cleavage by the mitochondrial processing peptidase generates long isoforms from eight messenger RNA (mRNA) splice forms, whereas further cleavages at protease sites S1 and S2 generate short forms. Using OPA1-null cells, we developed a cellular system to study how individual OPA1 splice forms function in mitochondrial fusion. Only mRNA splice forms that generate a long isoform in addition to one or more short isoforms support substantial mitochondrial fusion activity. On their own, long and short OPA1 isoforms have little activity, but, when coexpressed, they functionally complement each other. Loss of mitochondrial membrane potential destabilizes the long isoforms and enhances the cleavage of OPA1 at S1 but not S2. Cleavage at S2 is regulated by the i-AAA protease Yme1L. Our results suggest that mammalian cells have multiple pathways to control mitochondrial fusion through regulation of the spectrum of OPA1 isoforms.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle Material
Chan, David C.0000-0002-0191-2154
Additional Information:© 2007 The Rockefeller University Press. Submitted: 19 April 2007. Accepted: 25 July 2007. Published online 20 August 2007. We thank Drs. Lorena Griparic and Alex van der Bliek for communicating results before publication and for providing the anti-OPA1 antibody. This work was supported by National Institutes of Health grant GM062967 to D.C. Chan. Z. Song is supported by an Elizabeth Ross postdoctoral fellowship. Fig. S1 shows that OPA1-null cells expressing a single OPA1 RNA splice form have extensive fusion activity in the PEG cell hybrid assay. Online supplemental material is available at
Funding AgencyGrant Number
Issue or Number:5
PubMed Central ID:PMC2064540
Record Number:CaltechAUTHORS:SONjcb07
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8656
Deposited By: Archive Administrator
Deposited On:02 Sep 2007
Last Modified:24 Feb 2020 10:30

Repository Staff Only: item control page