First Author | Barbier-Torres L | Year | 2024 |
Journal | Int J Biol Sci | Volume | 20 |
Issue | 4 | Pages | 1218-1237 |
PubMed ID | 38385082 | Mgi Jnum | J:345709 |
Mgi Id | MGI:7608909 | Doi | 10.7150/ijbs.90104 |
Citation | Barbier-Torres L, et al. (2024) S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver. Int J Biol Sci 20(4):1218-1237 |
abstractText | MCJ (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 (MATalpha1), 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 MATalpha1 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 MATalpha1 and SAMe in reducing hepatic MCJ expression. |