The main focus of the laboratory is mitochondrial fatty acid oxidation. The organization
of the pathway for mitochondrial fatty acid oxidation is of particular interest
as a potential site for control of the system. Mitochondrial contact sites contain
the protein translocases for protein translocation into the mitochondria and the
peripheral benzodiazepine receptor. We have data that support the localization of
key enzymes, such as the long-chain acyl-CoA synthetase and carnitine palmitoyltransferase
of fatty acid oxidation to these contact sites. We have proposed a fatty acid/carnitine
shuttle through the contact sites. The characterization of this shuttle coupled
with the determination of its localization within the mitochondria will be essential
steps
During ischemia/reperfusion in the elderly heart there is increased myocardial damage
compared to adult controls. There is a decrease in the sensitivity of carnitine
palmitoyl-transferase-I to a competitive inhibitor, malonyl-CoA, without a change
in the total activity under this experimental protocol. We have investigated the
mitochondrial changes that occur during ischemia in the elderly rat heart. There
is a decrease in the activity of complex III, ubiquinone-cytochrome c oxidoreductase,
only in the interfibrillar mitochondria in the elderly heart and the activity does
not change in those mitochondria located underneath the sarcolemmal membrane (subsarcolemmal
mitochondria). The defect in the interfibrillar mitochondria involves the binding
of cytochrome c to complex III and is not due to a decrease in the catalytic subunits.
We are proposing to determine the molecular mechanisms underlining the oxidative
damage to complex III and to the enzymes of fatty acid oxidation. We have recently
purchased an electrospray mass spectrometer and currently are examining the determination
of peptides following oxidative damage using the mass spectrometer.
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