Ischemia-reperfusion injury (IRI) is a common complication in diverse clinical settings, including myocardial infarction, stroke, organ transplantation and major surgery. Its pathological core lies in the metabolic disruption caused by blood flow cessation, followed by oxidative stress, inflammatory cascades and cell death upon reperfusion. Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme best known for its role in aldehyde detoxification, has emerged as an important endogenous protective factor in IRI. ALDH2 limits the accumulation of toxic lipid peroxidation products, preserves mitochondrial function and attenuates oxidative and inflammatory damage in multiple organs. In parallel, ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been increasingly recognised as a key execution pathway in IRI. Increasing evidence suggests a close intersection between ALDH2 and ferroptosis. This review aims to systematically summarise the interplay between ALDH2 and ferroptosis in IRI, further explore their involvement in other forms of regulated cell death and highlight their points of convergence. Collectively, available data suggest that targeting ALDH2 may represent a promising strategy for limiting ferroptosis and reducing tissue damage in IRI.
Han et al. (Sun,) studied this question.