S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver

dc.contributor.authorBarbier-Torres, Lucía
dc.contributor.authorChhimwal, Jyoti
dc.contributor.authorKim, So Yeon
dc.contributor.authorRamani, Komal
dc.contributor.authorRobinson, Aaron
dc.contributor.authorYang, Heping
dc.contributor.authorVan Eyk, Jenny
dc.contributor.authorLiangpunsakul, Suthat
dc.contributor.authorSeki, Ekihiro
dc.contributor.authorMato, José M.
dc.contributor.authorLu, Shelly C.
dc.contributor.departmentBiochemistry and Molecular Biology, School of Medicine
dc.date.accessioned2024-06-13T09:36:12Z
dc.date.available2024-06-13T09:36:12Z
dc.date.issued2024-01-27
dc.description.abstractMCJ (Methylation-Controlled J protein), an endogenous repressor of the mitochondrial respiratory chain, is upregulated in multiple liver diseases but little is known about how it is regulated. S-adenosylmethionine (SAMe), the biological methyl donor, is frequently depleted in chronic liver diseases. Here, we show that SAMe negatively regulates MCJ in the liver. While deficiency in methionine adenosyltransferase alpha 1 (MATα1), enzyme that catalyzes SAMe biosynthesis, leads to hepatic MCJ upregulation, MAT1A overexpression and SAMe treatment reduced MCJ expression. We found that MCJ is methylated at lysine residues and that it interacts with MATα1 in liver mitochondria, likely to facilitate its methylation. Lastly, we observed that MCJ is upregulated in alcohol-associated liver disease, a condition characterized by reduced MAT1A expression and SAMe levels along with mitochondrial injury. MCJ silencing protected against alcohol-induced mitochondrial dysfunction and lipid accumulation. Our study demonstrates a new role of MATα1 and SAMe in reducing hepatic MCJ expression.
dc.eprint.versionFinal published version
dc.identifier.citationBarbier-Torres L, Chhimwal J, Kim SY, et al. S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver. Int J Biol Sci. 2024;20(4):1218-1237. Published 2024 Jan 27. doi:10.7150/ijbs.90104
dc.identifier.urihttps://hdl.handle.net/1805/41511
dc.language.isoen_US
dc.publisherIvyspring
dc.relation.isversionof10.7150/ijbs.90104
dc.relation.journalInternational Journal of Biological Sciences
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.sourcePMC
dc.subjectMCJ
dc.subjectMATα1
dc.subjectS-adenosylmethionine
dc.subjectProtein methylation
dc.subjectAlcohol-associated liver disease
dc.subjectMitochondrial dysfunction
dc.titleS-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver
dc.typeArticle
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