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Endosomal trafficking participates in lipid droplet catabolism to maintain lipid homeostasis

Author

Listed:
  • Wang Peng

    (City University of Hong Kong Shenzhen Research Institute
    City University of Hong Kong
    Department of Biomedical Sciences, Cornell University
    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)

  • Shu Chen

    (City University of Hong Kong Shenzhen Research Institute
    Department of Chemistry, City University of Hong Kong)

  • Jingyu Ma

    (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)

  • Wenjie Wei

    (Core Research Facilities, Southern University of Science and Technology)

  • Naixin Lin

    (City University of Hong Kong Shenzhen Research Institute
    City University of Hong Kong)

  • Jinchao Xing

    (City University of Hong Kong Shenzhen Research Institute
    City University of Hong Kong)

  • Wenjing Guo

    (Analysis and Testing Center, Guangzhou Institute of Biomedicine and Health (GIBH) Chinese Academy of Sciences)

  • Heying Li

    (Analysis and Testing Center, Guangzhou Institute of Biomedicine and Health (GIBH) Chinese Academy of Sciences)

  • Liang Zhang

    (City University of Hong Kong Shenzhen Research Institute
    City University of Hong Kong)

  • Kuiming Chan

    (City University of Hong Kong Shenzhen Research Institute
    City University of Hong Kong)

  • Andrew Yen

    (Department of Biomedical Sciences, Cornell University)

  • Guangyu Zhu

    (City University of Hong Kong Shenzhen Research Institute
    Department of Chemistry, City University of Hong Kong)

  • Jianbo Yue

    (City University of Hong Kong Shenzhen Research Institute
    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
    College of Life Sciences, Wuhan University
    Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University)

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.

Suggested Citation

  • Wang Peng & Shu Chen & Jingyu Ma & Wenjie Wei & Naixin Lin & Jinchao Xing & Wenjing Guo & Heying Li & Liang Zhang & Kuiming Chan & Andrew Yen & Guangyu Zhu & Jianbo Yue, 2025. "Endosomal trafficking participates in lipid droplet catabolism to maintain lipid homeostasis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57038-8
    DOI: 10.1038/s41467-025-57038-8
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    References listed on IDEAS

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    1. Rajat Singh & Susmita Kaushik & Yongjun Wang & Youqing Xiang & Inna Novak & Masaaki Komatsu & Keiji Tanaka & Ana Maria Cuervo & Mark J. Czaja, 2009. "Autophagy regulates lipid metabolism," Nature, Nature, vol. 458(7242), pages 1131-1135, April.
    2. Alex M. Valm & Sarah Cohen & Wesley R. Legant & Justin Melunis & Uri Hershberg & Eric Wait & Andrew R. Cohen & Michael W. Davidson & Eric Betzig & Jennifer Lippincott-Schwartz, 2017. "Applying systems-level spectral imaging and analysis to reveal the organelle interactome," Nature, Nature, vol. 546(7656), pages 162-167, June.
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