-
Views
-
Cite
Cite
Sara Pich, Daniel Bach, Paz Briones, Marc Liesa, Marta Camps, Xavier Testar, Manuel Palacín, Antonio Zorzano, The Charcot–Marie–Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system, Human Molecular Genetics, Volume 14, Issue 11, 1 June 2005, Pages 1405–1415, https://doi.org/10.1093/hmg/ddi149
Close - Share Icon Share
Abstract
Mitofusin-2 (Mfn2) is a mitochondrial membrane protein that participates in mitochondrial fusion in mammalian cells and mutations in the Mfn2 gene cause Charcot–Marie–Tooth neuropathy type 2A. Here, we show that Mfn2 loss-of-function inhibits pyruvate, glucose and fatty acid oxidation and reduces mitochondrial membrane potential, whereas Mfn2 gain-of-function increases glucose oxidation and mitochondrial membrane potential. As to the mechanisms involved, we have found that Mfn2 loss-of-function represses nuclear-encoded subunits of OXPHOS complexes I, II, III and V, whereas Mfn2 overexpression induced the subunits of complexes I, IV and V. Obesity-induced Mfn2 deficiency in rat skeletal muscle was also associated with a decrease in the subunits of complexes I, II, III and V. In addition, the effect of Mfn2 overexpression on mitochondrial metabolism was mimicked by a truncated Mfn2 mutant that is inactive as a mitochondrial fusion protein. Our results indicate that Mfn2 triggers mitochondrial energization, at least in part, by regulating OXPHOS expression through signals that are independent of its role as a mitochondrial fusion protein.
