Fig. 6.

UPS-mediated protein degradation in ferroptosis. The ubiquitination of proteins is important for the initiation of ferroptosis, which is regulated by various E3 ubiquitin ligases and deubiquitinating enzymes (DUBs). The ubiquitin-proteasome system (UPS) is involved in the degradation and stability of key regulators governing iron metabolism (e.g., TFRC, LTF, and SLC40A1), autophagy (e.g., NCOA4, and ZFP36, and BECN1), antioxidant system (e.g., SLC7A11, GPX4, FSP1, DHODH, and GSTP1), and transcription (e.g., NFE2L2/NRF2 and HELLS/LSH), as well as other proteins, including ACLS4 and VDAC. Ub, ubiquitination.