Isola 2018 MiPschool Tromso C3
Event: MiPschool Tromso-Bergen 2018
AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme, which is a sensor and regulator of the energetic state of the cell. Its activation results, among others, in increase of glucose uptake, mitochondrial fatty acid oxidation and mitochondrial biogenesis. The role of AMPK for mitochondrial function in cardiac tissue has not been deeply investigated. The purpose of this study was to assess whether the loss of AMPK in heart induces any alterations in mitochondrial physiology and whether potential changes are gender specific. Heart-specific double (α1 and α2 subunits) AMPK deletion was obtained in a model of a conditional tamoxifen-inducible KO mouse. Experiments were carried out with heart mitochondria, isolated from control and KO mice, both male and female. Mitochondrial respiration was measured with a Clark-type electrode, with substrates for Complex I (glutamate, malate), CII (succinate), CIV (TMPD), and with palmitoyl carnitine and dinitrophenole (DNP) as uncoupling agent. Enzymatic activities of Complex I and carnitine palmitoyl transferase 1 and 2 were assessed by a spectrophotometric assay. In addition, markers of mitochondrial density, such as citrate synthase activity have been analyzed. Our results show that AMPK-deficiency results in defects in OXPHOS and altered mitochondrial mass, and that some of these changes are gender-specific. The data indicate that loss of cardiac AMPK has some consequences already observed for skeletal muscle, but also additional effects. In particular, they reveal sex-specific responses possibly related to sex-specific metabolic differences in the heart.
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, Gender
Organism: Mouse Tissue;cell: Heart Preparation: Isolated mitochondria
Pathway: N, CIV, NS HRR: Oxygraph-2k Event: C3, Oral
Isola R(1), Dubouchaud H(2), Viollet B(3), Tokarska-Schlattner M(2), Schlattner U(2)
- Dept Biological Sciences, Univ Cagliari, Italy
- Lab Fundamental and Applied Bioenergetics (LBFA), Univ Grenoble Alpes
- Inst Cochin, Univ Paris Descartes, Sorbonne Paris Cité, Paris, France. – [email protected]
Short Scientific Mission (STSM) within the European Union Framework Programme Horizon 2020 COST Action CA15203 MitoEAGLE.