2. Academic Validation
  3. LipoID profiles lipid droplet interactions and identifies interorganelle regulators

LipoID profiles lipid droplet interactions and identifies interorganelle regulators

  • Nat Chem Biol. 2026 Jan 9. doi: 10.1038/s41589-025-02127-4.
Hengke Guo # 1,  Wang Wan # 1,  Yanan Huang # 2,  Nan Zhao # 1,  Ci Wu 3,  Bowen Zhong 1,  Rui Sun 1 4,  Huan Feng 1 4,  Jing Yan 1 5,  Di Shen 1,  Xuepeng Dong 5,  Qun Zhao 6,  Xin Zhang 7,  Lihua Zhang 8,  Yu Liu 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Medical Proteomics, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
  • 2 Department of Chemistry, Westlake University, Hangzhou, Zhejiang, China.
  • 3 School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, China.
  • 4 University of Chinese Academy of Sciences, Beijing, China.
  • 5 The Second Hospital of Dalian Medical University, Dalian, China.
  • 6 State Key Laboratory of Medical Proteomics, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China. [email protected].
  • 7 Department of Chemistry, Westlake University, Hangzhou, Zhejiang, China. [email protected].
  • 8 State Key Laboratory of Medical Proteomics, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China. [email protected].
  • 9 State Key Laboratory of Medical Proteomics, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China. [email protected].
  • # Contributed equally.
PMID: 41513856 DOI: 10.1038/s41589-025-02127-4
Abstract

Lipid droplets (LDs) dynamically interact with Other organelles, such as mitochondria, in surveillance of cellular metabolic homeostasis. The transient nature of LDs, however, poses technical challenges to snapshot molecular information underlying these interactions. Herein, we present a small-molecule-based photocatalytic protein proximity labeling method (named LipoID) to enable in situ labeling, capturing and profiling of the LD-interacting proteome. This method is enabled by a set of LD-targeting probes designed to catalyze protein modifications nearby LDs using nucleophilic substrates. Profiled by liquid chromatography-tandem mass spectrometry, LipoID identifies tethered interorganellar interactions, particularly with mitochondria, in addition to reliable capture of validated LD biomarkers (for example, perilipins (PLINs)). Coupled with comparative proteomics, LipoID discovers mitochondrial voltage-dependent anion channel 3 as a potential regulator of LD-mitochondria proximity through interacting with PLIN3 on LDs. Further metabolomics analysis suggested remodeled lipid metabolism in line with the LD-mitochondria interaction. Together, LipoID enables in situ profiling of the LD interactome and reveals interorganellar regulation.

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