CK-666 protects against ferroptosis and renal ischemia-reperfusion injury through a microfilament-independent mechanism.

ABSTRACT: Ferroptosis is a type of regulated cell death driven by iron-dependent accumulation of lipid peroxidation, exhibiting unique morphological changes. While actin microfilaments are crucial for various cellular processes, including morphogenesis, motility, endocytosis, and cell death, their role in ferroptosis remains unclear. Here, our study reveals that actin microfilaments undergo remodeling and disassembly during ferroptosis. Interestingly, inhibitors that target actin microfilament remodeling do not affect cell sensitivity to ferroptosis, with the exception of CK-666 and its structural analog CK-636. Mechanistically, CK-666 attenuates ferroptosis independently of its canonical function in inhibiting the Arp2/3 complex. Further investigation revealed that CK-666 modulates the ferroptotic

SUBMITTER: Hu Q 

PROVIDER: S-EPMC11625328 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature