Mitochondrial biogenesis in mammals: The role of endogenous nitric oxide

Enzo Nisoli, Emilio Clementi, Clara Paolucci, Valeria Cozzi, Cristina Tonello, Clara Sciorati, Renata Bracale, Alessandra Valerio, Maura Francolini, Salvador Moncada, Michele O. Carruba

    Research output: Contribution to journalArticlepeer-review


    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.
    Original languageEnglish
    Pages (from-to)896-899
    Number of pages3
    Issue number5608
    Publication statusPublished - 7 Feb 2003


    • 3T3 Cells
    • 8-Bromo Cyclic Adenosine Monophosphate/pharmacology
    • Adipocytes/*metabolism/ultrastructure
    • Adipose Tissue, Brown/cytology/metabolism/ultrastructure
    • Animals
    • Cold Temperature
    • Cyclic GMP/metabolism
    • DNA, Mitochondrial/metabolism
    • DNA-Binding Proteins/metabolism
    • Eating
    • Energy Metabolism
    • Female
    • HeLa Cells
    • High Mobility Group Proteins
    • Humans
    • Male
    • Mice
    • Mice, Knockout
    • Mitochondria/*metabolism/ultrastructure
    • *Mitochondrial Proteins
    • Motor Activity
    • NF-E2-Related Factor 1
    • Nitric Oxide/*physiology
    • Nitric Oxide Synthase/genetics/*metabolism
    • Nitric Oxide Synthase Type II
    • Nitric Oxide Synthase Type III
    • Nuclear Proteins/metabolism
    • Nuclear Respiratory Factors
    • Oligonucleotides, Antisense/pharmacology
    • Oxadiazoles/pharmacology
    • Oxygen Consumption
    • Penicillamine/*analogs & derivatives/pharmacology
    • Quinoxalines/pharmacology
    • RNA, Messenger/genetics/metabolism
    • Rats
    • Signal Transduction
    • Trans-Activators/metabolism
    • Transcription Factors/metabolism
    • U937 Cells
    • Weight Gain


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