title: Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity.
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.
authors.affiliation: Parc Cientific de Barcelona, Facultat de Biologia, Universitat de Barcelona, Barcelona 08028, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bach
authors.forename: Sara
authors.initials: S
authors.lastname: Pich
authors.forename: Francesc X
authors.initials: FX
authors.lastname: Soriano
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vega
authors.forename: Bernhard
authors.initials: B
authors.lastname: Baumgartner
authors.forename: Josep
authors.initials: J
authors.lastname: Oriola
authors.forename: Jens R
authors.initials: JR
authors.lastname: Daugaard
authors.forename: Jorge
authors.initials: J
authors.lastname: Lloberas
authors.forename: Marta
authors.initials: M
authors.lastname: Camps
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.forename: Rémi
authors.initials: R
authors.lastname: Rabasa-Lhoret
authors.forename: Harriet
authors.initials: H
authors.lastname: Wallberg-Henriksson
authors.forename: Martine
authors.initials: M
authors.lastname: Laville
authors.forename: Manuel
authors.initials: M
authors.lastname: Palacín
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Francisca
authors.initials: F
authors.lastname: Rivera
authors.forename: Martin
authors.initials: M
authors.lastname: Brand
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases; D005786:Gene Expression Regulation; D006801:Humans; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human