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Acetylomic and Lipidomic Profiling of Mice with Doxorubicin Induced Cardiomyopathy: A Cardiometabolic Disease Attenuated by Sirtuin-3

ABSTRACT: Doxorubicin (DOX) is a chemotherapeutic agent known for dose-dependent cardiotoxicity. Sirtuin 3 (SIRT3), a lysine deacetylase, regulates enzymatic function within mitochondria. DOX decreases SIRT3 levels, causing differential acetylation of cardiac mitochondrial enzymes. In this study, we evaluated M3-SIRT3 (shortened, not mitochondrial targeted), M1-SIRT3 (full length, mitochondrial localized), and non-transgenic mice treated with DOX (8.0mg/kg/week). M1-SIRT3 expression reduced mitochondrial acetylation and prevented DOX-induced cardiac remodelling and dysfunction. Acetyl-proteomics identified altered acetylation of mitochondrial enzymes involved in fatty acid metabolism.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Vernon W. Dolinsky

PROVIDER: MSV000095212 | MassIVE | Tue Jul 02 07:12:00 BST 2024

REPOSITORIES: MassIVE

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