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Transcriptional changes impact hepatic proteome in autophagy‐impaired liver

Authors :
Kamal Baral
Spandan Joshi
Adriana Lopez
Gavisha Mugon
Aroma Chanda
Arya A. Chandrasheker
Cameron Hinton
Kapil Thapa
Arissa Mercer
Leah Spade
Gang Liu
Bhupal Prasad Bhetwal
Jia Fang
Bilon Khambu
Source :
FEBS Open Bio, Vol 14, Iss 11, Pp 1851-1863 (2024)
Publication Year :
2024
Publisher :
Wiley, 2024.

Abstract

Hepatic proteomes are intricately controlled through biosynthesis, extracellular secretion, and intrahepatic degradation. Autophagy governs lysosome‐mediated intrahepatic degradation and the hepatic proteome. When autophagy is impaired, it leads to the accumulation of intrahepatic proteins, causing proteinopathy. This study investigates whether autophagy can modulate the hepatic proteome non‐degradatively. Utilizing conditional, inducible, and hepatotoxin models of hepatic autophagy impairment, we assessed the overall hepatic proteome expression using Coomassie brilliant blue (CBB) staining and liquid chromatography–tandem mass spectrometry (LC/MS). We pinpointed and confirmed four specific hepatic proteins—Cps1, Ahcy, Ca3, and Gstm1—that were selectively modified in autophagy‐deficient livers. Expression of Cps1, Ahcy, and Ca3 were significantly reduced, while Gstm1 expression increased in livers with autophagy impairment. Interestingly, these changes in hepatic protein levels were not due to defective autophagic degradation but were associated with alterations in mRNA transcript levels. Moreover, as a result of autophagic dysfunction, sustained activation of the nuclear erythroid‐derived 2‐like 2 (Nrf2) transcription factor, transcriptionally regulated the mRNA levels of these proteins. Our findings indicate that autophagy can influence hepatic proteins not solely via traditional degradative routes but also through non‐degradative transcriptional processes by modulating Nrf2.

Details

Language :
English
ISSN :
22115463
Volume :
14
Issue :
11
Database :
Directory of Open Access Journals
Journal :
FEBS Open Bio
Publication Type :
Academic Journal
Accession number :
edsdoj.22a957af6fd64d09bc842ccbc286b605
Document Type :
article
Full Text :
https://doi.org/10.1002/2211-5463.13898