Alterations in the mitochondrial regulatory pathways constituted by the nuclear co-factors PGC-1α or PGC-1β and mitofusin 2 in skeletal muscle in type 2 diabetes
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- 作者：Antonio Zorzano ; Marí ; a Isabel Herná ; ndez-Alvarez ; Manuel Palací ; n ; Geltrude Mingrone
- 关键词：Mitochondrial regulatory pathway ; Skeletal muscle ; Type 2 diabetes ; Mitofusin ; Insulin resistance
- 刊名：Biochimica et Biophysica Acta (BBA)/Bioenergetics
- 出版年：2010
- 出版时间：June-July 2010
- 年：2010
- 卷：1797
- 期：6-7
- 页码：1028-1033
- 全文大小：245 K
文摘
Muscle mitochondrial metabolism is regulated by a number of factors, many of which are responsible for the transcription of nuclear genes encoding mitochondrial proteins such as PPARδ, PGC-1α or PGC-1β. Recent evidence indicates that proteins participating in mitochondrial dynamics also regulate mitochondrial metabolism. Thus, in cultured cells the mitochondrial fusion protein mitofusin 2 (Mfn2) stimulates respiration, substrate oxidation and the expression of subunits involved in respiratory complexes. Mitochondrial dysfunction has been reported in skeletal muscle of type 2 diabetic patients. Reduced mitochondrial mass and defective activity has been proposed to explain this dysfunction. Alterations in mitochondrial metabolism may be crucial to account for some of the pathophysiological traits that characterize type 2 diabetes. Skeletal muscle of type 2 diabetic patients shows reduced expression of PGC-1α, PGC-1β, and Mfn2. In addition, a differential response to bilio-pancreatic diversion-induced weight loss in non-diabetic and type 2 diabetic patients has been reported. While non-diabetic morbidly obese subjects showed an increased expression of genes encoding Mfn2, PGC-1α, PGC-1β, PPARδ or SIRT1 in response to bariatric surgery-induced weight loss, no effect was detected in type 2 diabetic patients. These observations suggest the existence of a heritable component responsible for the abnormal control of the expression of genes encoding for modulators of mitochondrial biogenesis/metabolism, and which may participate in the development of the disease.