CIDE proteins and their regulatory mechanisms in lipid droplet fusion and growth

Abstract

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.

LncRNASnhg3Aggravates Hepatic Steatosis via PPARγ Signaling

“…Overexpression of CD36 in hepatocytes increased FFAs uptake and TG storage; conversely, its deletion ameliorated hepatic steatosis and insulin resistance in DIO mice (Rada et al, 2020). Additionally, CIDEA/C can also regulate various aspects of lipid homeostasis, including lipid storage, lipolysis, and lipid secretion (Xu et al, 2024). As a transcription regulator of Cd36 and Cidea/c , peroxisome proliferator-activated receptor γ (PPARγ) plays a crucial role in MASLD progression (Matsusue et al, 2008, Skat-Rordam et al, 2019, Lee et al, 2018, Lee et al, 2023b, Lee et al, 2021, Puri et al, 2008).…”