Ferroptosis as the Universal Selenoprotein Axis Failure Mechanism: GPx4-Selenium and FSP1-CoQ10 as Two Complementary Anti-Ferroptotic Defense Systems Across Multiple Organ Systems

This paper proposes that ferroptosis — iron-dependent, lipid peroxidation-driven cell death — represents the final common cell death pathway of Selenoprotein Axis failure across kidney, cochlear, pulmonary, cardiac, hepatic, and neurological tissues. The GPx4-selenium system (System 1) and the FSP1-CoQ10 system (System 2) are complementary non-redundant defenses. Simultaneous depletion of both produces compounded ferroptosis vulnerability. A February 2026 study in Cell Death & Disease confirmed selenomethionine as a dual-mechanism ferroptosis inhibitor that mitigated cisplatin-induced AKI in vivo. All claims are hypothesis-level requiring prospective clinical investigation.