Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis.
Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic tissues. Germline ablation of Sirt3 has major metabolic consequences, including increased susceptibility to metabolic damage and oxidative stress after high fat feeding. In order to determine the contribution of liver and skeletal muscle to these phenotypes, we generated muscle-specific Sirt3 (Sirt3(skm-/-)) and liver-specific Sirt3 (Sirt3(hep-/-)) knock-out mice. Despite a marked global hyperacetylation of mitochondrial proteins, Sirt3(skm-/-) and Sirt3(hep-/-) mice did not manifest any overt metabolic phenotype under either chow or high fat diet conditions. Similarly, there was no evidence for increased oxidative stress in muscle or liver when Sirt3 was ablated in a tissue-specific manner. These observations suggest that the mitochondrial hyperacetylation induced by Sirt3-deletion in a tissue specific manner is not necessarily linked to mitochondrial dysfunction and does not recapitulate the metabolic abnormalities observed in the germline Sirt3 knock-out mice.
Laboratory of Integrative and Systems Physiology-LISP/NCEM, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne-EPFL, 1015 Lausanne, Switzerland.
Pablo J
PJ
Fernandez-Marcos
Ellen H
EH
Jeninga
Carles
C
Canto
Taoufiq
T
Harach
Vincent C J
VC
de Boer
Penelope
P
Andreux
Norman
N
Moullan
Eija
E
Pirinen
Hiroyasu
H
Yamamoto
Sander M
SM
Houten
Kristina
K
Schoonjans
Johan
J
Auwerx
D000107:Acetylation; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056566:Sirtuin 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
D000255:Adenosine Triphosphate; D002331:Carnitine; D005978:Glutathione; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D056566:Sirtuin 3; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C525046:Sirt3 protein, mouse; C116917:acylcarnitine