Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria.
Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria.
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DOI：
10.1016/j.cell.2012.09.010
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发表时间：
2012-10-12
期刊：
影响因子：
64.5
通讯作者：
Kirichok Y
中科院分区：
文献类型：
--
作者：
Fedorenko A;Lishko PV;Kirichok Y
线粒体解偶联蛋白1（UCP 1）负责棕色脂肪组织（BAT）的非颤抖性产热。在被长链脂肪酸（LCFA）激活后，UCP 1增加线粒体内膜（IMM）的电导，使BAT线粒体产生热量而不是ATP。尽管UCP 1是线粒体阴离子载体家族（SLC 25）的成员，但据信UCP 1通过一种长期未解决的不寻常机制转运H+。在这里，我们实现了直接膜片钳测量UCP 1电流从IMM的BAT线粒体。我们发现UCP 1是一个LCFA阴离子/H+同向转运体。然而，LCFA阴离子不能从UCP 1解离，由于它们的疏水尾部建立的疏水相互作用，UCP 1有效地作为由LCFA激活的H+载体。类似的LCFA依赖性跨膜H+转运机制可能被其他SLC 25成员采用，并负责各种组织中的线粒体解偶联和代谢效率的调节。
Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). Upon activation by long-chain fatty acids (LCFAs), UCP1 increases the conductance of the inner mitochondrial membrane (IMM) to make BAT mitochondria generate heat rather than ATP. Despite being a member of the family of mitochondrial anion carriers (SLC25), UCP1 is believed to transport H+ by an unusual mechanism that has long remained unresolved. Here, we achieved direct patch-clamp measurements of UCP1 currents from the IMM of BAT mitochondria. We show that UCP1 is an LCFA anion/H+ symporter. However, the LCFA anions cannot dissociate from UCP1 due to hydrophobic interactions established by their hydrophobic tails, and UCP1 effectively operates as an H+ carrier activated by LCFA. A similar LCFA-dependent mechanism of transmembrane H+ transport may be employed by other SLC25 members and be responsible for mitochondrial uncoupling and regulation of metabolic efficiency in various tissues.
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影响因子：
64.8
作者：
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通讯作者：
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DOI：
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发表时间：
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