The Role of Mitochondrial Thioesterase-I, Uncoupling Protein-3, and CD36 in Cardiac Mitochondria
Year: 2008
Type: article
Abstract: Cardiac dysfunction and cardiomyopathy are associated with excessive accumulation of lipids in the heart.This condition can be mimicked by cardiac specific overexpression of peroxisome proliferator-activated receptor α (PPARα).Mitochondrial thioesterase I (MTE-I), a mitochondrial matrix protein whose expression is controlled by PPARα, deesterifies long chain acyl-CoAs into coenzyme A and fatty acid anions (FA -), thus it may play a role in reducing mitochondrial accumulation of toxic long chain acyl-CoAs and preventing lipotoxic cardiomyopathy.It is unclear how the generated FA -leave the mitochondrial matrix, but two mitochondrial proteins capable of exporting FA -have recently been identified: uncoupling protein 3 (UCP3) and fatty acid translocase (FAT) CD36.While it has been shown that diabetes or pharmacological activation of PPARα up-regulate mRNA expression of MTE-I and UCP3, little is known about the effects on protein expression or FA -export from mitochondria.Thus the goal of this dissertation is to elucidate the roles of MTE-I, UCP3, and CD36 in cardiac mitochondria, specifically examining the effects of diabetes and PPARα stimulation.First we studied the effects of treatment with the PPARα agonist fenofibrate or streptozotocin-induced diabetes on MTE-I and UCP3 protein expression and activity in isolated cardiac mitochondria in rats.Both diabetes and fenofibrate increased cardiac
Author: Kristen L. King
Institution: Case Western Reserve University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2521192171