Muscle or liver-specific Sirt3 deficiency induces hyperacetylation of mitochondrial proteins without affecting global metabolic homeostasis
| Autor: | Fernandez-Marcos Pablo J., Jeninga Ellen H., Canto Carles, Harach Taoufiq, De Boer Vincent C J, Andreux Penelope, Moullan Norman, Pirinen Eija, Yamamoto Hiroyasu, Houten Sander M., Schoonjans Kristina, Auwerx Johan |
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| Přispěvatelé: | Laboratory Genetic Metabolic Diseases, Paediatric Metabolic Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Mouse Gene Expression Mitochondrion medicine.disease_cause Mice Adenosine Triphosphate 0302 clinical medicine Sirtuin 3 Homeostasis Mice Knockout 0303 health sciences Ampk Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Acetylation Glutathione Mitochondria medicine.anatomical_structure Liver Sirtuin Female Oxidation-Reduction medicine.drug medicine.medical_specialty SIRT3 Blotting Western Activation Biology Stress Article Mitochondrial Proteins Superoxide dismutase 03 medical and health sciences Carnitine Internal medicine medicine Animals Life Science Obesity Energy-Expenditure Muscle Skeletal 030304 developmental biology Superoxide Dismutase Skeletal muscle Molecular biology Diet Mice Inbred C57BL Deacetylase Endocrinology biology.protein Energy Metabolism Reactive Oxygen Species Acids 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Scientific reports, 2. Nature Publishing Group Scientific Reports 2 (2012) Scientific Reports, 2 Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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 skm-/- and Sirt3 hep 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. |
| Databáze: | OpenAIRE |
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