Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Koentges, C; Pfeil, K; Schnick, T; Wiese, S; Dahlbock, R; Cimolai, MC; Meyer-Steenbuck, M; Cenkerova, K; Hoffmann, MM; Jaeger, C; Odening, KE; Kammerer, B; Hein, L; Bode, C; Bugger, H.
SIRT3 deficiency impairs mitochondrial and contractile function in the heart.
Basic Res Cardiol. 2015; 110(4): 36-36.
Doi: 10.1007/s00395-015-0493-6
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Bugger Heiko Matthias
- Co-Autor*innen der Med Uni Graz
- Pfeil Katharina
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Sirtuin 3 (SIRT3) is a mitochondrial NAD(+)-dependent deacetylase that regulates energy metabolic enzymes by reversible protein lysine acetylation in various extracardiac tissues. The role of SIRT3 in myocardial energetics and in the development of mitochondrial dysfunction in cardiac pathologies, such as the failing heart, remains to be elucidated. To investigate the role of SIRT3 in the regulation of myocardial energetics and function SIRT3(-/-) mice developed progressive age-related deterioration of cardiac function, as evidenced by a decrease in ejection fraction and an increase in enddiastolic volume at 24 but not 8 weeks of age using echocardiography. Four weeks following transverse aortic constriction, ejection fraction was further decreased in SIRT3(-/-) mice compared to WT mice, accompanied by a greater degree of cardiac hypertrophy and fibrosis. In isolated working hearts, a decrease in cardiac function in SIRT3(-/-) mice was accompanied by a decrease in palmitate oxidation, glucose oxidation, and oxygen consumption, whereas rates of glycolysis were increased. Respiratory capacity and ATP synthesis were decreased in cardiac mitochondria of SIRT3(-/-) mice. HPLC measurements revealed a decrease of the myocardial ATP/AMP ratio and of myocardial energy charge. Using LC-MS/MS, we identified increased acetylation of 84 mitochondrial proteins, including 6 enzymes of fatty acid import and oxidation, 50 subunits of the electron transport chain, and 3 enzymes of the tricarboxylic acid cycle. Lack of SIRT3 impairs mitochondrial and contractile function in the heart, likely due to increased acetylation of various energy metabolic proteins and subsequent myocardial energy depletion.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Citric Acid Cycle -
- Energy Metabolism -
- Male -
- Mice -
- Mice, Knockout -
- Mitochondria, Heart - physiology
- Myocardial Contraction -
- Oxidative Phosphorylation -
- Sirtuin 3 - physiology
- Find related publications in this database (Keywords)
- Mitochondria
- Energetics
- Cardiac function
- Sirtuin 3