Mitochondrial dynamics as a bridge between mitochondrial dysfunction and insulin resistance.
Muscle from obese subjects or from type 2 diabetic patients show mitochondrial dysfunction, and this may participate in the insulin resistance in those conditions. The mechanisms involved in mitochondrial dysfunction are not completely understood. Dynamic mitochondrial filaments or networks form by mitochondrial fusion and fission events. There is substantial evidence that proteins participating in mitochondrial fusion or fission also have a role in metabolism. Thus, mitofusin-2 (Mfn2) a mitochondrial fusion protein, stimulates respiration, substrate oxidation and OXPHOS subunits expression. In this regard, muscle from obese subjects, or from type 2 diabetic patients, show a reduced expression of Mfn2 and, amelioration of insulin sensitivity by bariatric surgery is associated with an increased Mfn2 expression in muscle. Here, we propose the hypothesis that mitochondrial dynamics proteins play a role in mitochondrial dysfunction in obesity or in type 2 diabetes and that it may also participate in the development of insulin resistance.
Zorzano
Antonio
A
Institute for Research in Biomedicine, Baldiri Reixac, Barcelona, Spain. antonio.zorzano@irbbarcelona.org
Liesa
Marc
M
Palacín
Manuel
M
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D020558:GTP Phosphohydrolases; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology*; D047494:PPAR delta / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000378:metabolism
D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D047494:PPAR delta; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D019703:Calcineurin; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human