Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity.

TitleMitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity.
Publication TypeJournal Article
Year of Publication2003
AuthorsBach, D, Pich, S, Soriano, FX, Vega, N, Baumgartner, B, Oriola, J, Daugaard, JR, Lloberas, J, Camps, M, Zierath, JR, Rabasa-Lhoret, R, Wallberg-Henriksson, H, Laville, M, Palacín, M, Vidal, H, Rivera, F, Brand, M, Zorzano, A
JournalJ Biol Chem
Volume278
Issue19
Pagination17190-7
Date Published2003 May 09
ISSN0021-9258
KeywordsAnimals, Gene Expression Regulation, GTP Phosphohydrolases, Humans, Membrane Potentials, Membrane Proteins, Middle Aged, Mitochondria, Muscle, Mitochondrial Proteins, Muscle, Skeletal, Obesity, Rats, Rats, Zucker
Abstract

In many cells and specially in muscle, mitochondria form elongated filaments or a branched reticulum. We show that Mfn2 (mitofusin 2), a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells, is induced during myogenesis and contributes to the maintenance and operation of the mitochondrial network. Repression of Mfn2 caused morphological and functional fragmentation of the mitochondrial network into independent clusters. Concomitantly, repression of Mfn2 reduced glucose oxidation, mitochondrial membrane potential, cell respiration, and mitochondrial proton leak. We also show that the Mfn2-dependent mechanism of mitochondrial control is disturbed in obesity by reduced Mfn2 expression. In all, our data indicate that Mfn2 expression is crucial in mitochondrial metabolism through the maintenance of the mitochondrial network architecture, and reduced Mfn2 expression may explain some of the metabolic alterations associated with obesity.

DOI10.1074/jbc.M212754200
Alternate JournalJ. Biol. Chem.
Citation Key10.1074/jbc.M212754200
PubMed ID12598526