PC-TP/StARD2: Of membranes and metabolism.

PC-TP/StARD2: Of membranes and metabolism.
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DOI:
10.1016/j.tem.2010.02.001
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发表时间:
2010-07
影响因子:
10.9
通讯作者:
Cohen, David E.
Cohen, David E.
中科院分区:
医学1区
文献类型:
--
作者:
Kang, Hye Won;Wei, Jie;Cohen, David E.

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磷脂酰胆碱转移蛋白(PC-TP,a.k.a. StARD 2)结合磷脂酰胆碱并在体外催化其膜间转移和交换。PC-TP的结构包括一个疏水口袋和一个明确的头基结合位点,其基因表达受过氧化物酶体增殖物激活受体α(peroxisomeproliferatoractivatedreceptor α)调控。最近的研究揭示了PC-TP在脂质和葡萄糖代谢中的关键调节作用。值得注意的是,Pctp-/-小鼠对胰岛素作用敏感,并表现出更有效的棕色脂肪介导的产热作用。PC-TP似乎通过刺激硫酯酶超家族成员2(一种新表征的长链脂肪酰辅酶A硫酯酶)的活性来限制脂肪酸进入线粒体。由于PC-TP在脂质双层内区分磷脂酰胆碱,因此它可以作为将代谢调节与膜组成联系起来的传感器。
Phosphatidylcholine transfer protein (PC-TP, a.k.a. StARD2) binds phosphatidylcholines and catalyzes their intermembrane transfer and exchange in vitro. The structure of PC-TP comprises a hydrophobic pocket and a well-defined head-group binding site, and its gene expression is regulated by peroxisome proliferator activated receptor α. Recent studies have revealed key regulatory roles for PC-TP in lipid and glucose metabolism. Notably, Pctp−/− mice are sensitized to insulin action and exhibit more efficient brown fat-mediated thermogenesis. PC-TP appears to limit access of fatty acids to mitochondria by stimulating the activity of thioesterase superfamily member 2, a newly characterized long-chain fatty acyl-CoA thioesterase. Because PC-TP discriminates among phosphatidylcholines within lipid bilayers, it may function as a sensor that links metabolic regulation to membrane composition.
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