Novel role of FATP1 in mitochondrial fatty acid oxidation in skeletal muscle cells.
Carnitine palmitoyltransferase 1 (CPT1) catalyzes the first step in long-chain fatty acid import into mitochondria, and it is believed to be rate limiting for beta-oxidation of fatty acids. However, in muscle, other proteins may collaborate with CPT1. Fatty acid translocase/CD36 (FAT/CD36) may interact with CPT1 and contribute to fatty acid import into mitochondria in muscle. Here, we demonstrate that another membrane-bound fatty acid binding protein, fatty acid transport protein 1 (FATP1), collaborates with CPT1 for fatty acid import into mitochondria. Overexpression of FATP1 using adenovirus in L6E9 myotubes increased both fatty acid oxidation and palmitate esterification into triacylglycerides. Moreover, immunocytochemistry assays in transfected L6E9 myotubes showed that FATP1 was present in mitochondria and coimmunoprecipitated with CPT1 in L6E9 myotubes and rat skeletal muscle in vivo. The cooverexpression of FATP1 and CPT1 also enhanced mitochondrial fatty acid oxidation, similar to the cooverexpression of FAT/CD36 and CPT1. However, etomoxir, an irreversible inhibitor of CPT1, blocked all these effects. These data reveal that FATP1, like FAT/CD36, is associated with mitochondria and has a role in mitochondrial oxidation of fatty acids.
Departments of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Barcelona, Spain.
David
D
Sebastián
Maria
M
Guitart
Celia
C
García-Martínez
Caroline
C
Mauvezin
Josep M
JM
Orellana-Gavaldà
Dolors
D
Serra
Anna M
AM
Gómez-Foix
Fausto G
FG
Hegardt
Guillermina
G
Asins
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000378:metabolism; D050612:Fatty Acid Transport Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D021381:Protein Transport; D051381:Rats
D018955:CD36 Antigens; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; C493569:Slc27a1 protein, mouse; D002334:Carnitine O-Palmitoyltransferase; D003066:Coenzyme A Ligases