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比较蛋白质组学揭示,脂肪滴锚定的线粒体在棕色脂肪细胞中对寒冷更为敏感。

Comparative proteomics reveals that lipid droplet-anchored mitochondria are more sensitive to cold in brown adipocytes.

机构信息

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.

出版信息

Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Oct;1866(10):158992. doi: 10.1016/j.bbalip.2021.158992. Epub 2021 Jun 17.

DOI:10.1016/j.bbalip.2021.158992
PMID:34147658
Abstract

Brown adipose tissue (BAT) is specialized for uncoupled heat production through mitochondrion fueled majorly from fatty acids (FAs) of lipid droplets (LDs). How the interaction between the two organelles contributes the generation of heat remains elusive. Here, we report that LD-anchored mitochondria (LDAM) were observed in the BAT of mice raised at three different temperatures, 30 °C, 23 °C, and 6 °C. The biochemical analyses including Western blotting of electron transport chain subunits showed that LDAM were functional. Comparative proteomics analysis was conducted, which revealed differential expressions of proteins between LDAM and cytoplasmic mitochondria (CM) at different temperatures. Higher expressions of proteins at low temperature were observed for i) FA β-oxidation in LDAM including FA synthesis and uncoupling, ii) pseudo-futile cycle in CM, and iii) two shuttle systems: glycerol 3-phosphate in both CM and LDAM and citrate malate in CM. Together, these results suggest that LDs and LDAM form a preorganized and functional organelle complex that permits the rapid response to cold.

摘要

棕色脂肪组织(BAT)专门通过主要由脂滴(LDs)中的脂肪酸(FAs)供能的线粒体进行解偶联产热。这两个细胞器之间的相互作用如何促进热量产生仍然难以捉摸。在这里,我们报告在在 30°C、23°C 和 6°C 三种不同温度下饲养的小鼠的 BAT 中观察到 LD 锚定的线粒体(LDAM)。包括电子传递链亚基的 Western blot 在内的生化分析表明 LDAM 是功能性的。进行了比较蛋白质组学分析,结果表明 LDAM 和细胞质线粒体(CM)之间的蛋白质表达在不同温度下存在差异。在低温下观察到更高表达的蛋白质包括:i)LDAM 中的 FA β-氧化,包括 FA 合成和解偶联,ii)CM 中的假无效循环,以及 iii)两个穿梭系统:CM 和 LDAM 中的甘油 3-磷酸和 CM 中的柠檬酸苹果酸。总之,这些结果表明 LDs 和 LDAM 形成了一个预先组织好的功能性细胞器复合物,允许对寒冷快速做出反应。

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