Deubiquitinase OTUD5 as a Novel Protector against 4-HNE-Triggered Ferroptosis in Myocardial Ischemia/Reperfusion Injury.

ABSTRACT: Despite the development of advanced technologies for interventional coronary reperfusion after myocardial infarction, a substantial number of patients experience high mortality due to myocardial ischemia-reperfusion (MI/R) injury. An in-depth understanding of the mechanisms underlying MI/R injury can provide crucial strategies for mitigating myocardial damage and improving patient survival. Here, it is discovered that the 4-hydroxy-2-nonenal (4-HNE) accumulates during MI/R, accompanied by high rates of myocardial ferroptosis. The loss-of-function of aldehyde dehydrogenase 2 (ALDH2), which dissipates 4-HNE, aggravates myocardial ferroptosis, whereas the activation of ALDH2 mitigates ferroptosis. Mechanistically, 4-HNE targets glutathione peroxidase 4 (GPX4) for K48-linked polyubiquitin-rela

SUBMITTER: Liu L 

PROVIDER: S-EPMC10558642 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature