Evidence for a Mitochondrial Regulatory Pathway Defined by Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α, Estrogen-Related Receptor-α, and Mitofusin 2

Abstract

Here, we report an increase in Mfn2 gene expression under conditions of high energy expenditure mediated by PGC-1α, and we also demonstrate that PGC-1α stimulates Mfn2 gene expression and that this is caused by two elements on the promoter that bind ERRα. In addition, we show that Mfn2 loss of function attenuates the effects of PGC-1α on mitochondrial membrane potential and that cold exposure causes an additional increase in PGC-1α in skeletal muscle from mice that are heterozygous knock-out (KO) for Mfn2.

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