Identification of fatty acid translocase on human skeletal muscle mitochondrial membranes: essential role in fatty acid oxidation.
Fatty acid translocase (FAT/CD36) is a transport protein with a high affinity for long-chain fatty acids (LCFA). It was recently identified on rat skeletal muscle mitochondrial membranes and found to be required for palmitate uptake and oxidation. Our aim was to identify the presence and elucidate the role of FAT/CD36 on human skeletal muscle mitochondrial membranes. We demonstrate that FAT/CD36 is present in highly purified human skeletal mitochondria. Blocking of human muscle mitochondrial FAT/CD36 with the specific inhibitor sulfo-N-succimidyl-oleate (SSO) decreased palmitate oxidation in a dose-dependent manner. At maximal SSO concentrations (200 muM) palmitate oxidation was decreased by 95% (P<0.01), suggesting an important role for FAT/CD36 in LCFA transport across the mitochondrial membranes. SSO treatment of mitochondria did not affect mitochondrial octanoate oxidation and had no effect on maximal and submaximal carnitine palmitoyltransferase I (CPT I) activity. However, SSO treatment did inhibit palmitoylcarnitine oxidation by 92% (P<0.001), suggesting that FAT/CD36 may be playing a role downstream of CPT I activity, possibly in the transfer of palmitoylcarnitine from CPT I to carnitine-acylcarnitine translocase. These data provide new insight regarding human skeletal muscle mitochondrial fatty acid (FA) transport, and suggest that FAT/CD36 could be involved in the cellular and mitochondrial adaptations resulting in improved and/or impaired states of FA oxidation.
Bezaire
Veronic
V
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, ON, Canada. vbezaire@uoguelph.ca
Bruce
Clinton R
CR
Heigenhauser
George J F
GJ
Tandon
Narendra N
NN
Glatz
Jan F C
JF
Luiken
Joost J J F
JJ
Bonen
Arend
A
Spriet
Lawrence L
LL
D000328:Adult; D015153:Blotting, Western; D002210:Caprylates / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050612:Fatty Acid Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009829:Oleic Acids / Q000494:pharmacology; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology
D002210:Caprylates; D004791:Enzyme Inhibitors; D050612:Fatty Acid Transport Proteins; D009829:Oleic Acids; D013388:Succinimides; C120556:sulfo-N-succinimidyl oleate; D019308:Palmitic Acid; D002334:Carnitine O-Palmitoyltransferase; C031492:octanoic acid