PXD059979

PXD059979 is an original dataset announced via ProteomeXchange.

Title	Chemical probe-enabled lipid droplet proteomics
Description	Emerging evidence indicates that lipid droplets (LDs) play important roles in lipid metabolism, energy homeostasis, and cell stress management. Notably, dysregulation of LDs is tightly linked to numerous diseases, including lipodystrophies, cancer, obesity, atherosclerosis and others. The pivotal physiological roles of LDs have led to an exploration of research in recent years. The functions of LDs are inherently connected to the composition of their proteome. Current methods for profiling LD proteins mostly utilize LD fractionation including those based on proximity-based labeling techniques. Glob-al profiling of the LD proteome in live cells without isolation of LDs is still challenging. Herein, we disclose two small-molecule chemical probes, termed LDF and LDPL. Both LDF/LDPL are small in size, could freely and specifically migrate within the lipid context of LDs. Consequently, they were successfully used for live-cell fluorescence imaging of LDs and from animal tissues. We further showed that LDPL was capable of large-scale profiling of LD proteome without the need of LD isolation. By using LDPL, 1549 high-confidence proteins, most of which could be annotated to prominent LD func-tions, were next identified. Importantly, further validation studies by using representative “hit” proteins revealed that CHMP6 and PRDX4 could act as the lipophagy receptor and lipolysis suppressor, respectively. Our results thus confirmed for the first time that LDPL is a powerful chemical tool for in situ profiling of LD proteomes. With the ability to provide a deeper understanding of LD proteomics from the native cellular environments, our newly developed strategy may be used in future to decipher the dynamics and molecular mechanism of LDs in various diseases.
HostingRepository	PRIDE
AnnounceDate	2025-05-27
AnnouncementXML	Submission_2025-05-27_08:06:34.367.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Junzhe Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-20 07:58:32	ID requested
⏵ 1	2025-05-27 08:06:34	announced

10.1021/JACS.5C01710;

submitter keyword: Fluorescence imaging,Lipid droplet, Proteomic, Chemical probe, Labeling

Jigang Wang
contact affiliation	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences
contact email	jgwang@icmm.ac.cn
lab head
Junzhe Zhang
contact affiliation	Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences
contact email	jzzhang@icmm.ac.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059979
     1. Label: PRIDE project
     2. Name: Chemical probe-enabled lipid droplet proteomics