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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
7P01HL074237-10
Application #
8532026
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2013
Total Cost
$265,458
Indirect Cost
$28,831
Name
Henry Ford Health System
Department
Type
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
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