2. Academic Validation
  3. Endosomal trafficking participates in lipid droplet catabolism to maintain lipid homeostasis

Endosomal trafficking participates in lipid droplet catabolism to maintain lipid homeostasis

  • Nat Commun. 2025 Feb 24;16(1):1917. doi: 10.1038/s41467-025-57038-8.
Wang Peng # 1 2 3 4,  Shu Chen # 1 5,  Jingyu Ma 4,  Wenjie Wei 6,  Naixin Lin 1 2,  Jinchao Xing 1 2,  Wenjing Guo 7,  Heying Li 7,  Liang Zhang 1 2,  Kuiming Chan 1 2,  Andrew Yen 3,  Guangyu Zhu 8 9,  Jianbo Yue 10 11 12 13
Affiliations

Affiliations

  • 1 City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
  • 2 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
  • 3 Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
  • 4 Division of Natural and Applied Sciences, Synear Molecular Biology Lab, Jiangsu Provincial University Key (Construction) Laboratory for Smart Diagnosis and Treatment of Lung Cancer, Duke Kunshan University, Kunshan, China.
  • 5 Department of Chemistry, City University of Hong Kong, Hong Kong, China.
  • 6 Core Research Facilities, Southern University of Science and Technology, Shenzhen, China.
  • 7 Analysis and Testing Center, Guangzhou Institute of Biomedicine and Health (GIBH) Chinese Academy of Sciences, Guangzhou, China.
  • 8 City University of Hong Kong Shenzhen Research Institute, Shenzhen, China. guangzhu@cityu.edu.hk.
  • 9 Department of Chemistry, City University of Hong Kong, Hong Kong, China. guangzhu@cityu.edu.hk.
  • 10 City University of Hong Kong Shenzhen Research Institute, Shenzhen, China. jianbo.yue@dukekunshan.edu.cn.
  • 11 Division of Natural and Applied Sciences, Synear Molecular Biology Lab, Jiangsu Provincial University Key (Construction) Laboratory for Smart Diagnosis and Treatment of Lung Cancer, Duke Kunshan University, Kunshan, China. jianbo.yue@dukekunshan.edu.cn.
  • 12 College of Life Sciences, Wuhan University, Wuhan, China. jianbo.yue@dukekunshan.edu.cn.
  • 13 Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China. jianbo.yue@dukekunshan.edu.cn.
  • # Contributed equally.
PMID: 39994216 DOI: 10.1038/s41467-025-57038-8
Abstract

The interplay between lipid droplets (LDs) and endosomes remains unknown. Here, we screen and synthesize AP1-coumarin, an LD-specific probe, by conjugating a Fluorescent Dye coumarin to a triazine compound AP1. AP1-coumarin labels all stages of LDs in live cells and markedly induces the accumulation of enlarged RAB5-RAB7 double-positive intermediate endosomes. The AP1-coumarin-labeled LDs contact these intermediate endosomes, with some LDs even being engulfed in them. When LD biogenesis is inhibited, the ability of AP1-coumarin to label LDs is markedly reduced, and the accumulation of enlarged intermediate endosomes is abolished. Moreover, blocking the biogenesis of LDs decreases the number of late endosomes while increasing the number of early endosomes and inhibits the endosomal trafficking of low-density lipoprotein (LDL) and transferrin. Correspondingly, interference with RAB5 or RAB7, either through knockdown or using dominant-negative mutants, inhibits LD catabolism, whereas the expression of a RAB7 constitutively active mutant accelerates LD catabolism. Additionally, CCZ1 knockdown not only induces the accumulation of intermediate endosomes but also inhibits LD catabolism. These results collectively suggest that LDs and endosomes interact and influence each other's functions, and endosomal trafficking participates in the catabolic process of LDs to maintain lipid homeostasis.

Figures
Products