| First Author | Lu Z | Year | 2011 |
| Journal | EMBO Rep | Volume | 12 |
| Issue | 8 | Pages | 840-6 |
| PubMed ID | 21720390 | Mgi Jnum | J:174774 |
| Mgi Id | MGI:5141159 | Doi | 10.1038/embor.2011.121 |
| Citation | Lu Z, et al. (2011) SIRT3-dependent deacetylation exacerbates acetaminophen hepatotoxicity. EMBO Rep 12(8):840-6 |
| abstractText | Acetaminophen/paracetamol-induced liver failure-which is induced by the binding of reactive metabolites to mitochondrial proteins and their disruption-is exacerbated by fasting. As fasting promotes SIRT3-mediated mitochondrial-protein deacetylation and acetaminophen metabolites bind to lysine residues, we investigated whether deacetylation predisposes mice to toxic metabolite-mediated disruption of mitochondrial proteins. We show that mitochondrial deacetylase SIRT3(-/-) mice are protected from acetaminophen hepatotoxicity, that mitochondrial aldehyde dehydrogenase 2 is a direct SIRT3 substrate, and that its deacetylation increases acetaminophen toxic-metabolite binding and enzyme inactivation. Thus, protein deacetylation enhances xenobiotic liver injury by modulating the binding of a toxic metabolite to mitochondrial proteins. |
