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Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide
Enzo Nisoli1, Emilio Clementi, Clara Paolucci
1Department of Preclinical Sciences, Center for Study and Research on Obesity, Luigi Sacco Hospital, University of Milan, Milan 20157, Italy. enzo.nisoli@unimi.it
Abstract:
Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS-/-) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice. Thus, a nitric oxide-cGMP-dependent pathway controls mitochondrial biogenesis and body energy balance.
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