Capture of the Mouse Organ Membrane Proteome Specificity in Peptidisc Libraries

Antony, Frank; Brough, Zora; Zhao, Zhiyu; Duong van Hoa, Franck

doi:10.1021/acs.jproteome.3c00825

“…As we reported recently, a protein was considered to be liver-specific ( i.e. organ enriched) when its relative abundance is heightened at least 2.5-fold (Log 2 ) compared to another organ, here the lung [39]. Through this assessment, the peptidisc identified 146 liver-specific proteins of which 80 were classified as IMPs ( Figure 1B and Table S1 ).…”

Section: Resultsmentioning

confidence: 84%

“…We recently reported the characterization of the mouse organ membrane proteome using the peptidisc method [39]. Here, we evaluated the method’s efficiency compared to the recently introduced SP4 method [40].…”

Section: Resultsmentioning

confidence: 99%

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

Antony,

Brough,

Orangi

et al. 2024

Preprint

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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.

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“…As we reported recently, a protein was considered to be liver-specific (i.e. organ enriched) when its relative abundance is heightened at least 2.5-fold (Log2) compared to another organ, here the lung [39]. Through this assessment, the peptidisc identified 146 liver-specific proteins of which 80 were classified as IMPs (Figure 1B and Table S1).…”

Section: Performance Of the Peptidisc And Sp4 Methods In Identifying ...mentioning

confidence: 80%

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

Antony,

Brough,

Orangi

et al. 2024

Preprint

0

View full text Add to dashboard Cite

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.

show abstract

Sensitive Profiling of Mouse Liver Membrane Proteome Dysregulation Following a High‐Fat and Alcohol Diet Treatment

Antony,

Brough,

Orangi

et al. 2024

Proteomics

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Alcohol consumption and high‐fat (HF) diets often coincide in Western society, resulting in synergistic negative effects on liver function. Although studies have analyzed the global protein expression in the context of alcoholic liver disease (ALD) and metabolic dysfunction‐associated steatotic liver disease (MASLD), none has offered specific insights on liver dysregulation at the membrane proteome level. Membrane‐specific profiling of metabolic and compensatory phenomena is usually overshadowed in conventional proteomic workflows. In this study, we use the Peptidisc method to isolate and compare the membrane protein (MP) content of the liver with its unique biological functions. From mice fed with an HF diet and ethanol in drinking water, we annotate over 1500 liver proteins with half predicted to have at least one transmembrane segment. Among them, we identify 106 integral MPs that are dysregulated compared to the untreated sample. Gene Ontology analysis reveals several dysregulated membrane‐associated processes like 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 upcoming steatosis of the liver model. Taken together, our Peptidisc‐based profiling of the diet‐dysregulated liver provides specific insights and hypotheses into the role of the transmembrane proteome in disease development, and flags desirable MPs for therapeutic and diagnostic targeting.

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Capture of the Mouse Organ Membrane Proteome Specificity in Peptidisc Libraries

Cited by 4 publications

References 50 publications

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

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

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

Sensitive Profiling of Mouse Liver Membrane Proteome Dysregulation Following a High‐Fat and Alcohol Diet Treatment

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