Metabolic characterization of a Sirt5 deficient mouse model.
Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD⁺-dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl phosphate synthase 1. Most recently, Sirt5 was reported to be the predominant protein desuccinylase and demalonylase in the mitochondria because the ablation of Sirt5 enhanced the global succinylation and malonylation of mitochondrial proteins, including many metabolic enzymes. In order to determine the physiological role of Sirt5 in metabolic homeostasis, we generated a germline Sirt5 deficient (Sirt5⁻/⁻) mouse model and performed a thorough metabolic characterization of this mouse line. Although a global protein hypersuccinylation and elevated serum ammonia during fasting were observed in our Sirt5⁻/⁻ mouse model, Sirt5 deficiency did not lead to any overt metabolic abnormalities under either chow or high fat diet conditions. These observations suggest that Sirt5 is likely to be dispensable for the metabolic homeostasis under the basal conditions.
Laboratory of Integrative and Systems Physiology (LISP/NCEM), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Jiujiu
J
Yu
Sushabhan
S
Sadhukhan
Lilia G
LG
Noriega
Norman
N
Moullan
Bin
B
He
Robert S
RS
Weiss
Hening
H
Lin
Kristina
K
Schoonjans
Johan
J
Auwerx
D000818:Animals; D059305:Diet, High-Fat; D005247:Feeding Behavior; D008297:Male; D055442:Metabolome / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010641:Phenotype; D015203:Reproducibility of Results; D037761:Sirtuins / Q000172:deficiency* / Q000378:metabolism; D014158:Transcription, Genetic
C542554:SIRT5 protein, mouse; D037761:Sirtuins