Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide.
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.
Nisoli
Enzo
E
Department of Preclinical Sciences, Center for Study and Research on Obesity, Luigi Sacco Hospital, University of Milan, Milan 20157, Italy. enzo.nisoli@unimi.it
Clementi
Emilio
E
Paolucci
Clara
C
Cozzi
Valeria
V
Tonello
Cristina
C
Sciorati
Clara
C
Bracale
Renata
R
Valerio
Alessandra
A
Francolini
Maura
M
Moncada
Salvador
S
Carruba
Michele O
MO
D016475:3T3 Cells; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D003080:Cold Temperature; D006152:Cyclic GMP / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D006367:HeLa Cells; D006609:High Mobility Group Proteins; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins; D009043:Motor Activity; D051265:NF-E2-Related Factor 1; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009687:Nuclear Proteins / Q000378:metabolism; D051264:Nuclear Respiratory Factors; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010101:Oxygen Consumption; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D020298:U937 Cells; D015430:Weight Gain
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; D051265:NF-E2-Related Factor 1; C495632:Nfe2l1 protein, rat; D009687:Nuclear Proteins; D051264:Nuclear Respiratory Factors; D016376:Oligonucleotides, Antisense; D010069:Oxadiazoles; D011810:Quinoxalines; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; C499631:TFAM protein, human; C081930:Tfam protein, mouse; C489030:Tfam protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C496316:Nos3 protein, rat; D010396:Penicillamine; D006152:Cyclic GMP