Zorzano 2014 Abstract MiP2014
|Metabolic implications of mitofusin 2 dysfunction.|
Zorzano A (2014)
Mitochondrial fusion and fission are key processes, regulating mitochondrial morphology. Mitochondrial fusion is catalyzed by Mfn1, Mfn2 and OPA1 in mammalian cells, whereas mitochondrial fission is operated by another set of proteins. Mfn2 protein seems to play a specifically complex role in mitochondria. It regulates mitochondrial morphology, and, in addition, it also controls endoplasmic reticulum morphology and function. Mfn2 expression is exquisitely regulated in skeletal muscle. It is up-regulated in skeletal muscle as response to chronic exercise and upon cold exposure. In contrast, Mfn2 is repressed in muscles from high-fat fed mice or in obese or type 2 diabetic individuals.
Changes in Mfn2 expression have a marked impact on mitochondrial metabolism. Skeletal muscles obtained from Mfn2 KO mice show a reduced respiratory control ratio, which occurs in the absence of significant changes in OXPHOS capacity and LEAK respiration. Mfn2-ablated soleus muscles also show reduced glucose oxidation and reduced expression of some OXPHOS subunits. Additional evidence, indicating that Mfn2 deficiency causes mitochondrial dysfunction, comes from studies in muscle cells in culture. The content of hydrogen peroxide was also enhanced in skeletal muscle upon Mfn2 depletion or in Mfn2-silenced muscle cells. These results occurred in the presence of a normal antioxidant defense.
Skeletal muscle Mfn2 KO mice also show susceptibility to develop insulin resistance in response to a high fat diet or to aging. In keeping with this, defective insulin signaling is detected in Mfn2-deficient mice treated with a high fat diet in response to in vivo insulin administration. Mfn2 knockdown muscle cells also show an impaired capacity to respond to insulin.
In summary, available data indicate that Mfn2 regulates metabolism and insulin signaling in skeletal muscles and may contribute to the pathophysiology in obesity and type 2 diabetes.
• O2k-Network Lab: ES Barcelona Zorzano A
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Exercise physiology;nutrition;life style Pathology: Diabetes, Obesity
Organism: Mouse Tissue;cell: Skeletal muscle
Coupling state: LEAK, OXPHOS
HRR: Oxygraph-2k Event: A2, Oral MiP2014
1-IRB Barcelona; 2-Univ Barcelona; 3-CIBERDEM, Inst Salud Carlos III; Barcelona, Spain. - [email protected]