GCLC and cancer: In support, our findings demonstrated the existence of novel succinylation modifications on GCLC, and moreover, oxidative stress can induce GCLC desuccinylation through enhancing vs. decreasing its association with desuccinylase SIRT2 and succinyltransferase P300, respectively, leading to a fast GCLC activation and consequently increased GSH synthesis, which endows cancer cells with phenotype of resistance to ferroptosis under oxidative stress condition (Fig. 6M).