Profiling the organ membrane proteome dysregulation in the context of
liver disease
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.