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Profiling the organ membrane proteome dysregulation in the context of liver disease
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  • Frank Antony,
  • Zora Brough,
  • Mona Orangi,
  • Hiroyuki Aoki,
  • Mohan Babu,
  • Franck Duong
Frank Antony
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Zora Brough
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Mona Orangi
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Hiroyuki Aoki
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Mohan Babu
University of Regina, Canada
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Franck Duong
UBC

Corresponding Author:[email protected]

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Abstract

Alcohol consumption and high-fat diets often coincide in Western society, exerting negative synergistic effects on the liver. While many studies have demonstrated the impact of ALD and NAFLD on organ protein expression, none have offered a comprehensive view of the dysregulation at the level of the membrane proteome. In this study, we utilize peptidisc and solvent precipitation (SP4) methods to isolate and compare the membrane protein content of the liver with its unique biological functions. Using mice treated with a high-fat diet and ethanol in drinking water, we identified 1,563 liver proteins, with 46% predicted to have a transmembrane segment. Among these, 106 integral membrane proteins are dysregulated compared to the untreated sample. Gene ontology analysis reveals several dysregulated membrane processes associated with lipid metabolism, cell adhesion, xenobiotic processing, and mitochondrial membrane formation. Pathways related to cholesterol and bile acid transport are also mutually affected, suggesting an adaptive mechanism to counter the steatosis of the liver model. Our peptidisc-based membrane proteome profiling thus emerges as an effective way to gain insights into the role of the transmembrane proteome in disease development, warranting further in-depth analysis of the individual effect of the identified dysregulated membrane proteins.
30 Mar 2024Submitted to PROTEOMICS
04 Apr 2024Submission Checks Completed
04 Apr 2024Assigned to Editor
07 May 2024Review(s) Completed, Editorial Evaluation Pending
06 Jul 2024Review(s) Completed, Editorial Evaluation Pending
06 Jul 20241st Revision Received
08 Jul 2024Reviewer(s) Assigned
18 Jul 2024Editorial Decision: Revise Minor
26 Jul 2024Review(s) Completed, Editorial Evaluation Pending
26 Jul 20242nd Revision Received
29 Jul 2024Reviewer(s) Assigned
14 Aug 2024Editorial Decision: Revise Minor
03 Sep 2024Review(s) Completed, Editorial Evaluation Pending
03 Sep 20243rd Revision Received
06 Sep 2024Editorial Decision: Accept