Nascent liver proteome reveals enzymes and transcription regulators under physiological and alcohol exposure conditions

Jiayu Gu, Lihui Lao, Linzhen Hu, Jia Zang, Chao Liu, Ruixi Wan, Ling Tang, Ying Yuan (), Yulin Chen () and Shixian Lin ()
Additional contact information
Jiayu Gu: The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University
Lihui Lao: Zhejiang University
Linzhen Hu: Zhejiang University
Jia Zang: Zhejiang University
Chao Liu: Zhejiang University
Ruixi Wan: Zhejiang University
Ling Tang: Zhejiang University
Ying Yuan: The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University
Yulin Chen: The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University
Shixian Lin: The Second Affiliated Hospital of Zhejiang University School of Medicine, Life Sciences Institute, Zhejiang University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract The liver proteome undergoes dynamic changes while performing hundreds of essential biological functions. Dysregulation of the liver proteome under alcoholic conditions leads to alcohol-associated liver disease (ALD), a major health challenge worldwide. There is an urgent need for quantitative and liver-specific proteome information in living animals to understand the pathophysiological dynamics of this largest solid organ. Here, we develop a comprehensive approach that specifically identifies the nascent proteome and preferentially enriches membrane proteins in living mouse hepatocytes and is broadly applicable to studies of the liver under various physiological and pathological conditions. In the ethanol-induced liver injury mouse model, the nascent proteome successfully identifies and validates a number of transcription regulators, enzymes, and protective chaperones involved in the molecular regulation of hepatic steatosis, in addition to almost all known regulatory proteins and pathways related to alcohol metabolism. We discover that Phb1/2 is an important transcription coregulator in the process of ethanol metabolism, and one identified fatty acid metabolism enzyme Acsl1/5, whose inhibition protects cells and mice from lipid accumulation, a key symptom of hepatic steatosis.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63212-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63212-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63212-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().