human trifunctional protein alpha links cardiolipin remodeling to beta-oxidation人类三功能性的心磷脂蛋白α链接改造机会.pdfVIP

Human Trifunctional Protein Alpha Links Cardiolipin Remodeling to Beta-Oxidation 1 1 1 2 3 William A. Taylor , Edgard M. Mejia , Ryan W. Mitchell , Patrick C. Choy , Genevieve C. Sparagna , Grant M. Hatch1,2* 1 Department of Pharmacology and Therapeutics, Center for Research and Treatment of Atherosclerosis, Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba, Canada, 2 Biochemistry and Medical Genetics, Center for Research and Treatment of Atherosclerosis, Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba, Canada, 3 Department of Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado, United States of America Abstract Cardiolipin (CL) is a mitochondrial membrane phospholipid which plays a key role in apoptosis and supports mitochondrial respiratory chain complexes involved in the generation of ATP. In order to facilitate its role CL must be remodeled with appropriate fatty acids. We previously identified a human monolysocardiolipin acyltransferase activity which remodels CL via acylation of monolysocardiolipin (MLCL) to CL and was identical to the alpha subunit of trifunctional protein (aTFP) lacking the first 227 amino acids. Full length aTFP is an enzyme that plays a prominent role in mitochondrial b-oxidation, and in this study we assessed the role, if any, which this metabolic enzyme plays in the remodeling of CL. Purified human recombinant aTFP exhibited acyl-CoA acyltransferase activity in the acylation of MLCL to CL with linoleoyl-CoA, oleoyl-CoA and palmitoyl-CoA as substrates. Expression of aTFP increased radioactive linoleate or oleate or palmitate incorporation into CL in HeLa cells. Expression of aTFP in Barth Syndro