A novel function for fatty acid translocase (FAT)/CD36: involvement in long chain fatty acid transfer into the mitochondria.
Fatty acid translocase (FAT)/CD36 is a long chain fatty acid transporter present at the plasma membrane, as well as in intracellular pools of skeletal muscle. In this study, we assessed the unexpected presence of FAT/CD36 in both subsarcolemmal and intermyofibril fractions of highly purified mitochondria. Functional assessments demonstrated that the mitochondria could bind (14)C-labeled palmitate, but could only oxidize it in the presence of carnitine. However, the addition of sulfo-N-succinimidyl oleate, a known inhibitor of FAT/CD36, resulted in an 87 and 85% reduction of palmitate oxidation in subsarcolemmal and intermyofibril fractions, respectively. Further studies revealed that maximal carnitine palmitoyltransferase I (CPTI) activity in vitro was inhibited by succinimidyl oleate (42 and 48% reduction). Interestingly, CPTI immunoprecipitated with FAT/CD36, indicating a physical pairing. Tissue differences in mitochondrial FAT/CD36 protein follow the same pattern as the capacity for fatty acid oxidation (heart >> red muscle > white muscle). Additionally, chronic stimulation of hindlimb muscles (7 days) increased FAT/CD36 expression and also resulted in a concomitant increase in mitochondrial FAT/CD36 content (46 and 47% increase). Interestingly, with acute electrical stimulation of hindlimb muscles (30 min), FAT/CD36 expression was not altered, but there was an increase in the mitochondrial content of FAT/CD36 compared with the non-stimulated control limb (35 and 37% increase). Together, these data suggest a role for FAT/CD36 in mitochondrial long chain fatty acid uptake and demonstrate system flexibility to match FAT/CD36 mitochondrial content with an increased capacity for fatty acid oxidation, possibly involving translocation of FAT/CD36 to the mitochondria.
Campbell
Shannon E
SE
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Tandon
Narendra N
NN
Woldegiorgis
Gebretateos
G
Luiken
Joost J F P
JJ
Glatz
Jan F C
JF
Bonen
Arend
A
D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism / Q000502:physiology*; D002210:Caprylates / Q000378:metabolism; D002331:Carnitine / Q000737:chemistry; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004594:Electrophysiology; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D027361:Organic Anion Transporters / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010168:Palmitates / Q000378:metabolism; D019308:Palmitic Acid / Q000737:chemistry / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D018955:CD36 Antigens; D002210:Caprylates; D005227:Fatty Acids; D027361:Organic Anion Transporters; D010168:Palmitates; D019308:Palmitic Acid; D002334:Carnitine O-Palmitoyltransferase; C031492:octanoic acid; D002331:Carnitine; D010100:Oxygen