Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide

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Science  07 Feb 2003:
Vol. 299, Issue 5608, pp. 896-899
DOI: 10.1126/science.1079368

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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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: enzo.nisoli{at}

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