| First Author | Soriano FX | Year | 2006 |
| Journal | Diabetes | Volume | 55 |
| Issue | 6 | Pages | 1783-91 |
| PubMed ID | 16731843 | Mgi Jnum | J:111879 |
| Mgi Id | MGI:3654994 | Doi | 10.2337/db05-0509 |
| Citation | Soriano FX, et al. (2006) Evidence for a Mitochondrial Regulatory Pathway Defined by Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha}, Estrogen-Related Receptor-{alpha}, and Mitofusin 2. Diabetes 55(6):1783-91 |
| abstractText | Mitofusin 2 (Mfn2) is a mitochondrial membrane protein that participates in mitochondrial fusion and regulates mitochondrial metabolism in mammalian cells. Here, we show that Mfn2 gene expression is induced in skeletal muscle and brown adipose tissue by conditions associated with enhanced energy expenditure, such as cold exposure or beta(3)-adrenergic agonist treatment. In keeping with the role of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha on energy expenditure, we demonstrate a stimulatory effect of PGC-1alpha on Mfn2 mRNA and protein expression in muscle cells. PGC-1alpha also stimulated the activity of the Mfn2 promoter, which required the integrity of estrogen-related receptor-alpha (ERRalpha)-binding elements located at -413/-398. ERRalpha also activated the transcriptional activity of the Mfn2 promoter, and the effects were synergic with those of PGC-1alpha. Mfn2 loss of function reduced the stimulatory effect of PGC-1alpha on mitochondrial membrane potential. Exposure to cold substantially increased Mfn2 gene expression in skeletal muscle from heterozygous Mfn2 knock-out mice, which occurred in the presence of higher levels of PGC-1alpha mRNA compared with control mice. Our results indicate the existence of a regulatory pathway involving PGC-1alpha, ERRalpha, and Mfn2. Alterations in this regulatory pathway may participate in the pathophysiology of insulin-resistant conditions and type 2 diabetes. |
