Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity.
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.
Bach
Daniel
D
Parc Cientific de Barcelona, Facultat de Biologia, Universitat de Barcelona, Barcelona 08028, Spain.
Pich
Sara
S
Soriano
Francesc X
FX
Vega
Nathalie
N
Baumgartner
Bernhard
B
Oriola
Josep
J
Daugaard
Jens R
JR
Lloberas
Jorge
J
Camps
Marta
M
Zierath
Juleen R
JR
Rabasa-Lhoret
Rémi
R
Wallberg-Henriksson
Harriet
H
Laville
Martine
M
Palacín
Manuel
M
Vidal
Hubert
H
Rivera
Francisca
F
Brand
Martin
M
Zorzano
Antonio
A
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
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human