Does iron loading of oxygen-sensing prolyl hydroxylases rather than random Fenton-driven radical formation drive programmed ferroptosis and degeneration in neurological diseases?

•Iron dyshomeostasis is linked to almost all neurological conditions.•Depletion of the antioxidant glutathione leads to iron dyshomeostasis.•Increased availability of iron could be sensed by oxygen sensing, HIF prolyl hydroxylases (HIF PHDs).•Increased activity of oxygen sensing HIF PHDs in normoxia not only reduces HIF but also increases ATF4-regulated ferroptotic gene expression.•Iron drives programmed cell death by activating iron-sensing HIF PHDs and not via non-specific Fenton Chemistry.