Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity.

Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Research Abstract Details 

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Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Abstract Text:

Naotada Ishihara,Yuka Eura,Katsuyoshi Mihara,

The mammalian homologues of yeast and Drosophila Fzo, mitofusin (Mfn) 1 and 2, are both essential for mitochondrial fusion and maintenance of mitochondrial morphology. Though the GTPase domain is required for Mfn protein function, the molecular mechanisms of the GTPase-dependent reaction as well as the functional division of the two Mfn proteins are unknown. To examine the function of Mfn proteins, tethering of mitochondrial membranes was measured in vitro by fluorescence microscopy using green fluorescence protein- or red fluorescent protein-tagged and Mfn1-expressing mitochondria, or by immunoprecipitation using mitochondria harboring HA- or FLAG-tagged Mfn proteins. These experiments revealed that Mfn1-harboring mitochondria were efficiently tethered in a GTP-dependent manner, whereas Mfn2-harboring mitochondria were tethered with only low efficiency. Sucrose density gradient centrifugation followed by co-immunoprecipitation revealed that Mfn1 produced oligomerized approximately 250 kDa and approximately 450 kDa complexes in a GTP-dependent manner. The approximately 450 kDa complex contained oligomerized Mfn1 from distinct apposing membranes (docking complex), whereas the approximately 250 kDa complex was composed of Mfn1 present on the same membrane or in the membrane-solubilized state (cis complex). These results were also confirmed using blue-native PAGE. Mfn1 exhibited higher activity for this reaction than Mfn2. Purified recombinant Mfn1 exhibited approximately eightfold higher GTPase activity than Mfn2. These findings indicate that the two Mfn proteins have distinct activities, and suggest that Mfn1 is mainly responsible for GTP-dependent membrane tethering.

Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Publishing Authors By Initials

N Ishihara,Y Eura,K Mihara,

For similar proteins: recombinant proteins: recombinant fusion proteins research abstracts see: proteins: recombinant proteins: recombinant fusion proteins research

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Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Journal Published:

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

Journal: Journal of cell science

VOLUME: 117

Page Numbers: 6535-46

Journal Abbreviation: J. Cell. Sci.

ISSN: 0021-9533

DAY: 30

MONTH: 11

YEAR: 2004

Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 52457

Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Keywords Mesh Terms:

KEYWORDS: Recombinant Fusion Proteins

MESH TERMS: physiology

Chemical & Substance for Abstract: Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity. Information

Substance Name: Mfn1 protein, human

Registry Number: EC 3.6.5.-

Grant and Affiliation Information for Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity.

AFFILIATION: Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.

Country: England

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MEDLINETA: J Cell Sci

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