Metabolomics-assisted Proteomics Reveals the Function of Lysine Succinylation and SIRT5 in Regulation of β-oxidation of Long-chain Fatty Acids

摘要

We found that in Sirt5 KO mouse, acyl-CoA and protein lysine succinylation were predominantly accumulated in heart. Proteomic studies identified many heart proteins regulated by SIRT5 and TFE-α contained the most succinylation sites found in the Sirt5 KO, indicative of TFE-α being a target of SIRT5. We observed a 30% reduction in amount of ATP in Sirt5 KO mice heart as compared to Sirt5 WT, suggesting regulation of TFE-α by SIRT5 functions for cellular energy production. We conclude that SIRT5 activates TFE-α through desuccinylation involved in β-oxidation of long chain fatty acids and ATP production, and metabolomics-assisted proteomic studies provides an effective approach for characterization of biological function of lysine succinylation regulated by SIRT5.