Identification of fatty acid translocase on human skeletal muscle mitochondrial membranes: essential role in fatty acid oxidation
Identification of fatty acid translocase on human skeletal muscle mitochondrial membranes: essential role in fatty acid oxidation
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DOI：
10.1152/ajpendo.00312.2005
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发表时间：
2006-03-01
影响因子：
5.1
通讯作者：
Spriet, LL
中科院分区：
文献类型：
--
作者：
Bezaire, V;Bruce, CR;Spriet, LL
脂肪酸转位酶（FAT/CD 36）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/CD 36的存在，并阐明其在人骨骼肌线粒体膜上的作用。我们证明，FAT/CD 36是存在于高度纯化的人骨骼线粒体。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/CD 36以剂量依赖性方式降低棕榈酸氧化。在最大SSO浓度（200 μ M）下，棕榈酸氧化降低95%（P < 0.01），表明FAT/CD 36在LCFA跨线粒体膜转运中起重要作用。SSO处理线粒体没有影响线粒体辛酸氧化，并没有影响最大和次最大肉毒碱棕榈酰转移酶I（CPTI）的活性。然而，SSO处理确实抑制了棕榈酰肉碱氧化92%（P < 0.001），表明FAT/CD 36可能在CPT I活性的下游发挥作用，可能在棕榈酰肉碱从CPTI转移到肉碱-酰基肉碱移位酶中。这些数据提供了关于人骨骼肌线粒体脂肪酸（FA）转运的新见解，并表明FAT/CD 36可能参与细胞和线粒体适应，导致FA氧化状态改善和/或受损。
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 mu M) 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 (CPTI) 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 CPTI 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.