Protein modification and degradation in ferroptosis
Yuan Wang,
Ding Yan,
Jinbao Liu,
Daolin Tang,
Xin Chen
Affiliations
Yuan Wang
Key Laboratory of Biological Targeting Diagnosis, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China; State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
Ding Yan
Key Laboratory of Biological Targeting Diagnosis, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China; State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China
Jinbao Liu
Key Laboratory of Biological Targeting Diagnosis, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China; State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China; Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 511436, China
Daolin Tang
Department of Surgery, UT Southwestern Medical Center, Dallas, 75390, USA; Corresponding author.
Xin Chen
Key Laboratory of Biological Targeting Diagnosis, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China; State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China; Corresponding author. Key Laboratory of Biological Targeting Diagnosis, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China
Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These proteins undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, and oxidative modification. These modifications play pivotal roles in regulating protein stability, activity, localization, and interactions, ultimately influencing both the buildup of iron and lipid peroxidation. In mammalian cells, regulators of ferroptosis typically undergo degradation via two principal pathways: the ubiquitin-proteasome system, which handles the majority of protein degradation, and autophagy, primarily targeting long-lived or aggregated proteins. This comprehensive review aims to summarize recent advances in the post-translational modification and degradation of proteins linked to ferroptosis. It also discusses strategies for modulating ferroptosis through protein modification and degradation systems, providing new insights into potential therapeutic applications for both cancer and non-neoplastic diseases.
