Cardiac mitochondria exist in two distinct populations wathin the myocyte, subsarcolemmal mitochondria (SSM), located beneath the sarcolemmal membrane, and interfibrillar mitochondria (IFM) that reside between the myofibrils. SSM are released by tissue homogenization, whereas the liberation of IFM requires a brief exposure of the resulting skinned myocytes to trypsin treatment. The two populations of mitochondria are differently affected under both physiological and pathophysiological conditions and thus requires to study of each individual population separately. The Mitochondrial/Mass Spec Core (Core D) will perform the following experiments as a service to the different Projects. 1. Isolate subsarcolemmal and interfibrillar mitochondria from experimental hearts;assess quality control. 2. Obtain samples of myocardium and isolated populations of SSM and IFM for electron transport chain complex analysis. 3. Obtain samples of heart, SSM, and IFM for lipid extraction and phospholipid analysis. Special attention is paid to cardiolipin (CL) analysis: CL content, CL species and CL oxidation. 4. Aquire heart tissue for analysis of acyl-CoAs and acylcarnitines with special emphasis on malonyl-CoA a key metabolite in switch in fuel utilization. 5. Carry out mass spectrometric analysis to identify posttranslational and oxidative modifications on ETC subunits, especially complex IV. 6. Perform structural analysis on cardiac tissue and cardiac SSM and IFM by transmission electron microscopy. 7. Isoprostane and oxidized low density lipoprotein (oxLDL) quantitation as a measure of in vivo oxidative stress. 8. Blue Native Electrophoresis will be done on mitochondria from Project 1 and 4.
Mitochondrial are the powerhouses and the cell. During heart failure an energy crises occurs in the heart and is related to the dysfunction of mitochondria. This Core will provide mitochondrial isolation from heart of dogs and mice under experimental conditions and perform analytical methods to support the 4 project within the Program Project Grant.
|Flori, Alessandra; Liserani, Matteo; Frijia, Francesca et al. (2015) Real-time cardiac metabolism assessed with hyperpolarized [1-(13) C]acetate in a large-animal model. Contrast Media Mol Imaging 10:194-202|
|Vimercati, Claudio; Qanud, Khaled; Mitacchione, Gianfranco et al. (2014) Beneficial effects of acute inhibition of the oxidative pentose phosphate pathway in the failing heart. Am J Physiol Heart Circ Physiol 306:H709-17|
|Mitacchione, Gianfranco; Powers, Jeffrey C; Grifoni, Gino et al. (2014) The gut hormone ghrelin partially reverses energy substrate metabolic alterations in the failing heart. Circ Heart Fail 7:643-51|
|Velez, Mauricio; Kohli, Smita; Sabbah, Hani N (2014) Animal models of insulin resistance and heart failure. Heart Fail Rev 19:1-13|
|Prosdocimo, Domenick A; Anand, Priti; Liao, Xudong et al. (2014) Kruppel-like factor 15 is a critical regulator of cardiac lipid metabolism. J Biol Chem 289:5914-24|
|Shekar, Kadambari Chandra; Li, Ling; Dabkowski, Erinne R et al. (2014) Cardiac mitochondrial proteome dynamics with heavy water reveals stable rate of mitochondrial protein synthesis in heart failure despite decline in mitochondrial oxidative capacity. J Mol Cell Cardiol 75:88-97|
|Clericò, Vito; Masini, Luca; Boni, Adriano et al. (2014) Water-dispersible three-dimensional LC-nanoresonators. PLoS One 9:e105474|
|Rosca, Mariana G; Tandler, Bernard; Hoppel, Charles L (2013) Mitochondria in cardiac hypertrophy and heart failure. J Mol Cell Cardiol 55:31-41|
|Hecker, Peter A; Lionetti, Vincenzo; Ribeiro Jr, Rogerio F et al. (2013) Glucose 6-phosphate dehydrogenase deficiency increases redox stress and moderately accelerates the development of heart failure. Circ Heart Fail 6:118-26|
|Galvao, Tatiana F; Khairallah, Ramzi J; Dabkowski, Erinne R et al. (2013) Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival. Am J Physiol Heart Circ Physiol 304:H12-21|
Showing the most recent 10 out of 139 publications