Bezaire Veronic, Bruce Clinton R, Heigenhauser George J F, Tandon Narendra N, Glatz Jan F C, Luiken Joost J J F, Bonen Arend, Spriet Lawrence L
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
Am J Physiol Endocrinol Metab. 2006 Mar;290(3):E509-15. doi: 10.1152/ajpendo.00312.2005. Epub 2005 Oct 11.
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.
脂肪酸转位酶（FAT/CD36）是一种对长链脂肪酸（LCFA）具有高亲和力的转运蛋白。最近在大鼠骨骼肌线粒体膜上发现了它，并且发现它是棕榈酸摄取和氧化所必需的。我们的目的是确定FAT/CD36在人骨骼肌线粒体膜上的存在情况并阐明其作用。我们证明FAT/CD36存在于高度纯化的人骨骼肌线粒体中。用特异性抑制剂磺基-N-琥珀酰亚胺油酸酯（SSO）阻断人肌肉线粒体FAT/CD36可使棕榈酸氧化呈剂量依赖性降低。在最大SSO浓度（200μM）时，棕榈酸氧化降低了95%（P<0.01），这表明FAT/CD36在长链脂肪酸跨线粒体膜转运中起重要作用。用SSO处理线粒体不影响线粒体辛酸氧化，对最大和亚最大肉碱棕榈酰转移酶I（CPT I）活性也无影响。然而，SSO处理确实使棕榈酰肉碱氧化降低了92%（P<0.001），这表明FAT/CD36可能在CPT I活性的下游发挥作用，可能参与将棕榈酰肉碱从CPT I转移至肉碱-酰基肉碱转位酶的过程。这些数据为人类骨骼肌线粒体脂肪酸（FA）转运提供了新的见解，并表明FAT/CD36可能参与导致脂肪酸氧化改善和/或受损状态的细胞和线粒体适应性变化。
