Ferroptosis has been reported as a unique form of cell death. However, in recent years, researchers have increasingly challenged the uniqueness of ferroptosis compared to other types of cell death. In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death, especially autophagy, via the autophagic process. Here, we observed that ferroptosis inducers (artesunate and erastin) and autophagy inducers (bortezomib and XIE62-1004) led to autophagosome formation via the endoplasmic reticulum (ER) stress response. Unlike XIE62-1004, artesunate, erastin, and bortezomib, which affect glutathione production or utilization, induced oxidative stress responses - an increase in the levels of heme oxygenase-1 and lipid peroxidation. Oxidative stress responses were attenuated by deletion of autophagy related gene-5 or treatment with autophagy inhibitors (bafilomycin and chloroquine). Our studies provide an overview of common death pathways - the ER stress response-associated autophagic process in ferroptosis and autophagy. We also highlight the role the glutathione redox system plays in the outcome of the autophagic process.

Citation Format: Yong J. Lee. Role of the glutathione antioxidant system in the autophagic process outcome [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1239.