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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
United States
Zip Code
Sabbah, Hani N; Gupta, Ramesh C; Singh-Gupta, Vinita et al. (2018) Abnormalities of Mitochondrial Dynamics in the Failing Heart: Normalization Following Long-Term Therapy with Elamipretide. Cardiovasc Drugs Ther 32:319-328
Lanfear, David E; Gibbs, Joseph J; Li, Jia et al. (2017) Targeted Metabolomic Profiling of Plasma and Survival in Heart Failure Patients. JACC Heart Fail 5:823-832
Maruyama, Sonomi; Nakamura, Kazuto; Papanicolaou, Kyriakos N et al. (2016) Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture. EMBO Mol Med 8:949-66
Sabbah, Hani N; Gupta, Ramesh C; Kohli, Smita et al. (2016) Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure. Circ Heart Fail 9:e002206
Ardell, J L; Andresen, M C; Armour, J A et al. (2016) Translational neurocardiology: preclinical models and cardioneural integrative aspects. J Physiol 594:3877-909
Kop, Willem J; Galvao, Tatiana F; Synowski, Stephen J et al. (2015) Effects of environmental stress following myocardial infarction on behavioral measures and heart failure progression: The influence of isolated and group housing conditions. Physiol Behav 152:168-74
Roul, David; Recchia, Fabio A (2015) Metabolic alterations induce oxidative stress in diabetic and failing hearts: different pathways, same outcome. Antioxid Redox Signal 22:1502-14
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
Recchia, Fabio A (2015) Revascularization of hibernating myocardium: uneven reflorescence after the drought. J Am Coll Cardiol 65:698-700
Trappanese, Danielle M; Liu, Yuchuan; McCormick, Ryan C et al. (2015) Chronic ?1-adrenergic blockade enhances myocardial ?3-adrenergic coupling with nitric oxide-cGMP signaling in a canine model of chronic volume overload: new insight into mechanisms of cardiac benefit with selective ?1-blocker therapy. Basic Res Cardiol 110:456

Showing the most recent 10 out of 166 publications