PI(4)P recruits CIDE proteins to promote the formation of unilocular lipid droplets during adipogenesis and hepatic steatosis
Abstract
Lipid droplets (LDs) are evolutionarily conserved organelles that play important roles in metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. The composition of LD surface phospholipids and their impact on LD growth and function remain to be defined. Phosphoinositides mark cellular organelles and regulate organellar function. Here, we demonstrate that PI(4)P decorates a subset of LDs to recruit and activate CIDE proteins. Enhanced expression of ORP2 and ORP5, LD-associated lipid transfer proteins that remove PI(4)P from LDs, abolished the localization and function of CIDE proteins. Blocking the synthesis of PI(4)P on the LD surface via knocking down PI4K2A also impaired the localization and function of CIDE proteins. In adipocytes, depleting PI(4)P dramatically reduced the size of LDs, as well as adipose tissue mass. In severe steatotic liver, depleting PI(4)P impeded LD enlargement. Our results thus identify a key function of LD surface PI(4)P under physiological conditions and unveil how CIDE proteins are recruited to LDs.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Jin Wu
Mingming Gao
Xiaoqin Wu
Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston
Yang Liu
Taiping Zhang
Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Yan Liang
State Key Laboratory of Fine Chemicals, School of Chemistry
Haixia Yang
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
Chengxin Ma
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
Youpi Ye
Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University
Chunmei Chang
Shanghai Key Laboratory of Metabolic Remodeling and Health, State Key Laboratory of Genetics and Development of Complex Phenotypes, Institute of Metabolism and Integrative Biology, School of Life Sciences, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
Peng Li
Feng-Jung Chen
Hongyuan Yang