Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle
Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle
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DOI：
10.1016/j.devcel.2023.01.007
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Shuai Chen
中科院分区：
文献类型：
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作者：
Qian Ouyang;Qiaoli Chen;Shunyuan Ke;Longfei Ding;Xinyu Yang;Ping Rong;Weikuan Feng;Ye Cao;Qi Wang;Min Li;Shu Su;Wen Wei;Minjun Liu;Jin Liu;Xu Zhang;John Zhong Li;Hong-Yu Wang;Shuai Chen
Dynamic interaction between lipid droplets (LDs) and mitochondria controls the mobilization of long-chain fatty acids (LCFAs) from LDs for mitochondrial b-oxidation in skeletal muscle in response to energy stress. However, little is known about the composition and regulation of the tethering complex mediating LD-mito- chondrion interaction. Here, we identify Rab8a as a mitochondrial receptor for LDs forming the tethering complex with the LD-associated PLIN5 in skeletal muscle. In rat L6 skeletal muscle cells, the energy sensor AMPK increases the GTP-bound active Rab8a that promotes LD-mitochondrion interaction through binding to PLIN5 upon starvation. The assembly of the Rab8a-PLIN5 tethering complex also recruits the adipose triglyceride lipase (ATGL), which couples LCFA mobilization from LDs with its transfer into mitochondria for b-oxidation. Rab8a deficiency impairs fatty acid utilization and decreases endurance during exercise in a mouse model. These findings may help to elucidate the regulatory mechanisms underlying the beneficial effects of exercise on lipid homeostasis control.
