PPIA as a central regulator in a novel cell death pathway activated by iron homeostasis and redox disruption in multiple myeloma

• DHA induces ferroptosis in multiple myeloma by disrupting iron homeostasis and redox balance, upregulating TFRC and HMOX1. • PPIA is identified as a novel redox-sensitive target of DHA; binding to oxidized PPIA elevates ROS and promotes ferroptotic cell death. • Combination of DHA with erastin synergistically enhances cytotoxicity and MM inhibition, suggesting a promising therapeutic strategy. • DHA also promotes T-cell activation and augments tumor suppression in a syngeneic mouse model, indicating potential immunomodulatory effects.