title: Fatty acid import into mitochondria.
abstract: The mitochondrial carnitine system plays an obligatory role in beta-oxidation of long-chain fatty acids by catalyzing their transport into the mitochondrial matrix. This transport system consists of the malonyl-CoA sensitive carnitine palmitoyltransferase I (CPT-I) localized in the mitochondrial outer membrane, the carnitine:acylcarnitine translocase, an integral inner membrane protein, and carnitine palmitoyltransferase II localized on the matrix side of the inner membrane. Carnitine palmitoyltransferase I is subject to regulation at the transcriptional level and to acute control by malonyl-CoA. The N-terminal domain of CPT-I is essential for malonyl-CoA inhibition. In liver CPT-I activity is also regulated by changes in the enzyme's sensitivity to malonyl-CoA. As fluctuations in tissue malonyl-CoA content are parallel with changes in acetyl-CoA carboxylase activity, which in turn is under the control of 5'-AMP-activated protein kinase, the CPT-I/malonyl-CoA system is part of a fuel sensing gauge, turning off and on fatty acid oxidation depending on the tissue's energy demand. Additional mechanism(s) of short-term control of CPT-I activity are emerging. One proposed mechanism involves phosphorylation/dephosphorylation dependent direct interaction of cytoskeletal components with the mitochondrial outer membrane or CPT-I. We have proposed that contact sites between the outer and inner mitochondrial membranes form a microenvironment which facilitates the carnitine transport system. In addition, this system includes the long-chain acyl-CoA synthetase and porin as components.
authors.affiliation: Department of Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kerner
authors.forename: C
authors.initials: C
authors.lastname: Hoppel
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018272:Porins / Q000378:metabolism; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D005227:Fatty Acids; D018272:Porins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D002331:Carnitine