NITRIC_OXIDE _i_cellbiologi

 

Science 7 February 2003:
Vol. 299. no. 5608, pp. 896 - 899
DOI: 10.1126/science.1079368

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Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide

Enzo Nisoli,12*dagger Emilio Clementi,34* Clara Paolucci,3 Valeria Cozzi,1 Cristina Tonello,1 Clara Sciorati,3 Renata Bracale,1 Alessandra Valerio,5 Maura Francolini,6 Salvador Moncada,7 Michele O. Carruba12

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.

1 Department of Preclinical Sciences, Center for Study and Research on Obesity, Luigi Sacco Hospital, University of Milan, Milan 20157, Italy.
2 Istituto Auxologico Italiano, Milan 20149, Italy.
3 DIBIT-H San Raffaele Institute, Milan 20132, Italy.
4 Department of Pharmaco-Biology, University of Calabria, Rende 87036, Italy.
5 Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia 25123, Italy.
6 Consiglio Nazionale delle Ricerche Institute of Neuroscience, Cellular and Molecular Pharmacology Section, Milan 20129, Italy.
7 The Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: enzo.nisoli@unimi.it

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POS5 Gene of Saccharomyces cerevisiae Encodes a Mitochondrial NADH Kinase Required for Stability of Mitochondrial DNA.

M. K. Strand, G. R. Stuart, M. J. Longley, M. A. Graziewicz, O. C. Dominick, and W. C. Copeland (2003)
Eukaryot. Cell 2, 809-820
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