Abstract
Insufficient intake of the essential trace element selenium can lead to cardiovascular disease through oxidative stress. The expression of Sirtuin 3 (Sirt3)/YME1-like 1 ATPase (YME1L1) deacetylase pathway related factors is highly sensitive to intracellular redox fluctuations. However, its functional role in selenium‑deficient (-Se) myocardial tissue remains unclear. A porcine model of selenium deficiency was established by feeding a diet containing 0.030 mg/kg selenium. To investigate the role of YME1L1 acetylation, YME1L1‑K237R and YME1L1‑K237Q plasmids were transfected into cardiomyocytes. Oxidative stress, myocardial structure, mitochondrial morphology, protein acetylation, and PANoptosis markers were evaluated using histology, transmission electron microscopy, immunoprecipitation, western blot, and qRT‑PCR. Selenium deficiency induced oxidative stress, which downregulated Sirt3 and increased YME1L1 acetylation at K237, leading to mitochondrial dysfunction characterized by impaired mitochondrial dynamics, reduced ATP production, and mtDNA release. The deacetylation‑mimetic YME1L1‑K237R mutant significantly rescued PANoptosis. These findings identify an oxidative stress‑mediated Sirt3/YME1L1 acetylation axis, with YME1L1‑K237 as the critical acetylation switch, as a novel driver of PANoptosis in selenium‑deficient myocardium, offering new insights into the cardiac function of selenium.