National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, South Korea.
Laboratory of Cell Metabolism, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Nat Commun. 2020 Jan 29;11(1):578. doi: 10.1038/s41467-019-14176-0.
Lipid droplets (LDs) are key subcellular organelles for regulating lipid metabolism. Although several subcellular organelles participate in lipid metabolism, it remains elusive whether physical contacts between subcellular organelles and LDs might be involved in lipolysis upon nutritional deprivation. Here, we demonstrate that peroxisomes and peroxisomal protein PEX5 mediate fasting-induced lipolysis by stimulating adipose triglyceride lipase (ATGL) translocation onto LDs. During fasting, physical contacts between peroxisomes and LDs are increased by KIFC3-dependent movement of peroxisomes toward LDs, which facilitates spatial translocations of ATGL onto LDs. In addition, PEX5 could escort ATGL to contact points between peroxisomes and LDs in the presence of fasting cues. Moreover, in adipocyte-specific PEX5-knockout mice, the recruitment of ATGL onto LDs was defective and fasting-induced lipolysis is attenuated. Collectively, these data suggest that physical contacts between peroxisomes and LDs are required for spatiotemporal translocation of ATGL, which is escorted by PEX5 upon fasting, to maintain energy homeostasis.
脂滴 (LDs) 是调节脂质代谢的关键亚细胞细胞器。虽然有几个亚细胞细胞器参与脂质代谢，但在营养剥夺时，亚细胞细胞器与 LDs 之间的物理接触是否参与脂解仍然难以捉摸。在这里，我们证明过氧化物酶体和过氧化物酶体蛋白 PEX5 通过刺激脂肪甘油三酯脂肪酶 (ATGL) 转位到 LDs 上来介导禁食诱导的脂解。在禁食期间，过氧化物酶体向 LDs 的 KIFC3 依赖性运动增加了过氧化物酶体和 LDs 之间的物理接触，从而促进了 ATGL 在 LDs 上的空间转位。此外，在存在禁食信号的情况下，PEX5 可以护送 ATGL 到过氧化物酶体和 LDs 之间的接触点。此外，在脂肪细胞特异性 PEX5 敲除小鼠中，ATGL 募集到 LDs 的缺陷和禁食诱导的脂解减弱。总之，这些数据表明，过氧化物酶体和 LDs 之间的物理接触对于 ATGL 的时空转位是必需的，在禁食时 PEX5 护送 ATGL 到 LDs，以维持能量平衡。
