Host: The Japanese Society of Toxicology
Polymyxin B (PMB), a last-line antibiotic used against multidrug-resistant bacteria, causes undesirable cytotoxic side effects, including nephrotoxicity and neurotoxicity. However, its mechanisms remain unknown. In this study, we found that the E3 ubiquitin ligase MKRN1 strongly protects cells from the toxicity of PMB by suppressing PMB-induced ferroptosis, a newly discovered iron-dependent cell death. Thus, our study identified MKRN1 as a key determinant of the toxicity of PMB, which may provide a new strategy to overcome the cytotoxic side effects of PMB.
