Proteomics

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Depletion of Mitochondrial Methionine Adenosyltransferase α1 Triggers Mitochondrial Dysfunction in Alcohol-Associated Liver Disease


ABSTRACT: Mitochondrial MATα1 is selectively depleted in alcohol-associated liver disease through a mechanism that involves the isomerase PIN1 and the kinase CK2. Alcohol activates CK2, which phosphorylates MATα1 at Ser114 facilitating interaction with PIN1, thereby inhibiting its mitochondrial localization. Blocking PIN1-MATα1 interaction increased mitochondrial MATα1 levels and protected against alcohol-induced mitochondrial dysfunction.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Liver Disease

SUBMITTER: Aleksandra Binek  

LAB HEAD: Shelly C. Lu

PROVIDER: PXD030383 | Pride | 2022-02-17

REPOSITORIES: Pride

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Publications


MATα1 catalyzes the synthesis of S-adenosylmethionine, the principal biological methyl donor. Lower MATα1 activity and mitochondrial dysfunction occur in alcohol-associated liver disease. Besides cytosol and nucleus, MATα1 also targets the mitochondria of hepatocytes to regulate their function. Here, we show that mitochondrial MATα1 is selectively depleted in alcohol-associated liver disease through a mechanism that involves the isomerase PIN1 and the kinase CK2. Alcohol activates CK2, which pho  ...[more]

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