DJ-1 inhibits ferroptosis in cerebral ischemia-reperfusion via ATF4/HSPA5 pathway.

DJ-1 has been confirmed to have neuroprotective effects. Ferroptosis is an iron-dependent programmed cell death mode associated with ischemic stroke. The ATF4/HSPA5 pathway has been shown to play an important role in the regulation of ferroptosis. To explore the role and possible mechanism of DJ-1 in regulating ferroptosis in cerebral ischemia-reperfusion injury. In this study, Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to simulate cerebral ischemia-reperfusion injury in vivo. Detected ferroptosis-related indicators and observed mitochondrial morphology in brain tissue using transmission electron microscopy. ATF4 was subsequently interfered to observe the effect of DJ-1 on ferroptosis. The results suggest that after interfering with DJ-1, the iron content and malondialdehyde (MDA) content of ferroptosis-related indicators increased, the GSH content decreased, and the mitochondrial structure was severely damaged. We then found that DJ-1 attenuated ferroptosis following ATF4 reduction. In this study, we found that the neuroprotective effect of DJ-1 is related to the inhibition of ferroptosis, and its molecular mechanism is closely related to the ATF4/HSPA5 pathway, which may play a key role in inhibiting brain ischemia-reperfusion (I/R) ferroptosis.