SIRT5 alleviate cardiomyocyte senescence in radiation-induced heart disease via desuccinylation of HADHB

SIRT5 deficiency caused widespread protein hypersuccinylation in cardiac tissue. Succinylation proteomic analysis revealed HADHB as the key SIRT5 target, with lysine 292 (K292) being the dominant succinylation site. Functional studies demonstrated that K292 succinylation impairs HADHB-mediated fatty acid β-oxidation, ultimately promoting cardiomyocyte senescence. These findings reveal a critical regulatory axis involving SIRT5-HADHB succinylation in the pathogenesis of radiation-induced cardiomyopathy, providing new insights into potential therapeutic strategies.