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Mitochondrial Biogenesis In Mammals: The Role Of Endogenous Nitric Oxide

E. Nisoli, E. Clementi, C. Paolucci, V. Cozzi, C. Tonello, C. Sciorati, R. Bracale, A. Valerio, M. Francolini, S. Moncada, M. Carruba
Published 2003 · Biology, Medicine

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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 γ coactivator 1α, 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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