小柯机器人

北京大学Yifu Qiu团队近期取得重要工作进展，他们研究发现线粒体钙单向转运体与UCP1结合形成促进产热的热转运体。相关论文于2022年8月16日在线发表于《细胞—代谢》杂志上。

研究人员表明线粒体钙单向转运体（MCU）通过必需的MCU调节器（EMRE）募集UCP1，在肾上腺素能刺激下形成MCU-EMRE-UCP1复合物。这种复合物的形成增加了线粒体钙的摄取，以加速三羧酸循环并提供更多促进非耦合呼吸的质子，起到产热单向转运体的作用。线粒体钙摄取1（MICU1）可能通过抑制产热单向转运体的形成负调节产热。因此，棕色脂肪细胞中Mcu或Emre的缺失会显著损害产热并加剧肥胖和代谢功能障碍。

值得注意的是，通过Micu1敲除或表达连接的EMRE-UCP1增强的产热单向转运体组装导致相反的表型。因此，研究人员发现了一种“热转运体”，它为产热中的UCP1操作提供驱动力，可用于对抗肥胖和相关的代谢紊乱。

据介绍，解偶联蛋白1 (UCP1)介导的适应性产热保护哺乳动物免受低温和代谢失调。线粒体钙是否以及如何调节这一过程尚不清楚。

附：英文原文

Title: The mitochondrial calcium uniporter engages UCP1 to form a thermoporter that promotes thermogenesis

Author: Kaili Xue, Dongmei Wu, Yushuang Wang, Yiheng Zhao, Hongyu Shen, Jingfei Yao, Xun Huang, Xinmeng Li, Zhao Zhou, Zihao Wang, Yifu Qiu

Issue&Volume: 2022-08-16

Abstract: Uncoupling protein 1 (UCP1)-mediated adaptive thermogenesis protects mammals against hypothermia and metabolic dysregulation. Whether and how mitochondrial calcium regulates this process remains unclear. Here, we show that mitochondrial calcium uniporter (MCU) recruits UCP1 through essential MCU regulator (EMRE) to form an MCU-EMRE-UCP1 complex upon adrenergic stimulation. This complex formation increases mitochondrial calcium uptake to accelerate the tricarboxylic acid cycle and supply more protons that promote uncoupled respiration, functioning as a thermogenic uniporter. Mitochondrial calcium uptake 1 (MICU1) negatively regulates thermogenesis probably through inhibiting thermogenic uniporter formation. Accordingly, the deletion of Mcu or Emre in brown adipocytes markedly impairs thermogenesis and exacerbates obesity and metabolic dysfunction. Remarkably, the enhanced assembly of the thermogenic uniporter via Micu1 knockout or expressing linked EMRE-UCP1 results in opposite phenotypes. Thus, we have uncovered a “thermoporter” that provides a driving force for the UCP1 operation in thermogenesis, which could be leveraged to combat obesity and associated metabolic disorders.

DOI: 10.1016/j.cmet.2022.07.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00310-2

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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