Institute of Metabolism and Integrative Biology, the Human Phenome Institute, Fudan University, and Zhongshan Hospital of Fudan University, Shanghai, China.
State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China.
Traffic. 2020 Jan;21(1):94-105. doi: 10.1111/tra.12717.
Dysregulation of lipid homeostasis leads to the development of metabolic disorders including obesity, diabetes, cardiovascular disease and cancer. Lipid droplets (LDs) are subcellular organelles vital in the maintenance of lipid homeostasis by coordinating lipid synthesis, lipid storage, lipid secretion and lipolysis. Under fed condition, free fatty acids (FFAs) are remodeled and esterified into neutral lipids by lipogenesis and stored in the LDs. The lipid storage capacity of LDs is controlled by its growth via local lipid synthesis or by LD fusion. During fasting, neutral lipids are hydrolyzed by lipolysis, released as FFAs and secreted to meet energy demand. Cell death-inducing DNA fragmentation factor alpha (DFFA)-like effector (CIDE) family proteins composed of Cidea, Cideb and Cidec/Fsp27 are ER- and LD-associated proteins and have emerged as important regulators of lipid homeostasis. Notably, when localized on the LDs, CIDE proteins enrich at the LD-LD contact sites (LDCSs) and control LD fusion and growth. Here, we summarize these recent advances made on the role of CIDE proteins in the regulation of lipid metabolism with a particular focus on the molecular mechanisms underlying CIDE-mediated LD fusion and growth.
脂质代谢失衡会导致多种代谢紊乱的发生，包括肥胖、糖尿病、心血管疾病和癌症。脂滴（LDs）是细胞内的细胞器，在维持脂质代谢平衡方面起着至关重要的作用，通过协调脂质合成、脂质储存、脂质分泌和脂解来实现这一目标。在进食状态下，游离脂肪酸（FFAs）通过脂肪生成被重塑并酯化形成中性脂质，并储存在 LD 中。LD 的脂质储存能力通过局部脂质合成或 LD 融合来控制。在禁食状态下，中性脂质通过脂解水解，释放出 FFAs 并分泌出去以满足能量需求。细胞死亡诱导 DNA 片段化因子α（DFFA）样效应物（CIDE）家族蛋白由 Cidea、Cideb 和 Cidec/Fsp27 组成，是内质网和 LD 相关蛋白，已成为脂质代谢平衡的重要调节因子。值得注意的是，当 CIDE 蛋白定位于 LD 上时，它们在 LD-LD 接触位点（LDCS）富集，并控制 LD 融合和生长。本文总结了 CIDE 蛋白在调节脂质代谢中的作用的最新进展，特别关注了 CIDE 介导的 LD 融合和生长的分子机制。
