State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
College of Future Technology, Peking University, Beijing, China.
FEBS Lett. 2024 May;598(10):1154-1169. doi: 10.1002/1873-3468.14823. Epub 2024 Feb 14.
The cell death-inducing DFF45-like effector (CIDE) proteins, including Cidea, Cideb, and Cidec/Fsp27, regulate various aspects of lipid homeostasis, including lipid storage, lipolysis, and lipid secretion. This review focuses on the physiological roles of CIDE proteins based on studies on knockout mouse models and human patients bearing CIDE mutations. The primary cellular function of CIDE proteins is to localize to lipid droplets (LDs) and to control LD fusion and growth across different cell types. We propose a four-step process of LD fusion, characterized by (a) the recruitment of CIDE proteins to the LD surface and CIDE movement, (b) the enrichment and condensate formation of CIDE proteins to form LD fusion plates at LD-LD contact sites, (c) lipid transfer through lipid-permeable passageways within the fusion plates, and (d) the completion of LD fusion. Lastly, we outline CIDE-interacting proteins as regulatory factors, as well as their contribution in LD fusion.
细胞死亡诱导 DFF45 样效应物（CIDE）蛋白，包括 Cidea、Cideb 和 Cidec/Fsp27，调节脂质稳态的各个方面，包括脂质储存、脂肪分解和脂质分泌。本综述基于敲除小鼠模型和携带 CIDE 突变的人类患者的研究，重点介绍了 CIDE 蛋白的生理作用。CIDE 蛋白的主要细胞功能是定位于脂滴（LDs）并控制不同细胞类型中 LD 的融合和生长。我们提出了 LD 融合的四步过程，其特征在于：（a）CIDE 蛋白募集到 LD 表面并发生 CIDE 运动；（b）CIDE 蛋白在 LD-LD 接触部位富集并形成凝聚体以形成 LD 融合板；（c）通过融合板内的脂质可渗透通道进行脂质转移；（d）LD 融合完成。最后，我们概述了 CIDE 相互作用蛋白作为调节因子及其在 LD 融合中的作用。
