biorxiv2026-10-09score 88
Sub-toxic iron sulfate depolarizes neuroblastoma mitochondria, raises proton leak, and cuts hydrogen peroxide
Mendonça, Rossignol, Amoedo, Oliveira and colleagues loaded SH-SY5Y neuroblastoma cells with 100 µM iron sulfate for 24 hours, a pulse that was not cytotoxic. Intracellular iron rose about four-fold. Mitochondria fragmented and lost membrane potential, yet mitochondrial content and OXPHOS coupling efficiency held. The only respiratory state that increased was proton leak. Total cellular oxidants and hydrogen peroxide output fell, ferritin rose, and the cells proliferated more while migrating less. The redox story is a leak-dependent drop in driving force that biophysically limits oxidant production, not a Fenton burst. The metal is loaded iron, stored in ferritin. Cluster nuclearity was not measured.