Control of lipid droplet fusion and growth by CIDE family proteins

Cell death-inducing DFF45-like effector (CIDE) family proteins including Cidea, Cideb and Cidec/Fsp27 are expressed in many different tissues and are known as lipid droplet (LD)-and ER-associated proteins. Systematic analyses using genetically modified animal models have demonstrated that CIDE proteins play important roles in regulating various aspects of lipid homeostasis, including lipid storage, lipolysis and lipid secretion. Recent research in ours and other laboratories has revealed that CIDE proteins are crucial regulators of LD fusion and growth in the adipose tissue, liver, skin and mammary glands. CIDE-mediated LD fusion and growth is different from other membrane fusions in that it requires CIDE proteins to be enriched and clustered at the LD-LD contact sites (LDCS). The enriched CIDE proteins then allow the recruitment of other proteins to the LDCS and the formation of potential fusion pores. Neutral lipids in the smaller LDs of the contacted pair are transferred to the larger LDs, owing to the internal pressure difference, thus resulting in the fusion and growth of the LDs. This review summarizes the physiological roles of CIDE proteins in controlling lipid homeostasis, insulin sensitivity and the development of metabolic diseases including obesity, diabetes and fatty liver, with a particular focus on the role of CIDE proteins in controlling LD fusion and growth. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.