Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism

作者：Daniel Q. Bach, Sara Pich, Francesc Xavier Soriano, Nathalie Véga, Bernhard Gregor Baumgartner, Josep Oriola, Jens R. Daugaard, Jorge Lloberas, Marta Camps, Juleen Rae Zierath, RÉMI P.R. RABASA-LHORET, Harriet Wallberg‐Henriksson, Martine Laville, Manuel Palacı́n, Hubert Vidal, Francisca Vazquez Rivera, Martin D. Brand, António Zorzano · 发表于：Journal of Biological Chemistry · 年份：2003 · DOI：10.1074/jbc.m212754200 · 被引用次数：834 · 研究领域：Mitochondrial Function and Pathology、Metabolism and Genetic Disorders、Adipose Tissue and Metabolism

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.