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

OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. Research Abstract Details 

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OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. Abstract Text:

Zhiyin Song,Hsiuchen Chen,Maja Fiket,Christiane Alexander,David C Chan,Zhiyin Song,Hsiuchen Chen,Maja Fiket,Christiane Alexander,David C Chan,

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.

OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. Publishing Authors By Initials

Z Song,H Chen,M Fiket,C Alexander,DC Chan,Z Song,H Chen,M Fiket,C Alexander,DC Chan,

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OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of cell biology

VOLUME: 178

Page Numbers: 749-55

Journal Abbreviation: J. Cell Biol.

ISSN: 0021-9525

DAY: 20

MONTH: 08

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 375356

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Grant and Affiliation Information for OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L.

AFFILIATION: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM062967

ACRONYM: GM

MEDLINETA: J Cell Biol

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