Ferroptosis is a mechanism of cell death that has possible roles in numerous diseases. Two new studies have identified hydropersulfides as potent inhibitors of O2-dependent membrane damage and destruction, and as potential regulators of ferroptosis.

Unregulated cellular iron, unchecked lipid peroxidation and loss of membrane integrity can result in ferroptotic cell death, and this process can have possible pathological consequences (for example, neurodegeneration and cardiac disease). Although ferroptosis can have undesirable outcomes, this may not always be the case. Indeed, ferroptosis may actually have positive roles in, for example, tumor suppression and immune surveillance1. Thus, an understanding of the control and regulation of ferroptosis can be vital to a complete understanding of disease etiology whether ferroptosis is causative or protective. It is known that ferroptosis results from alterations in oxidation chemistry (that is, lipid peroxidation occurs via membrane oxidation) and therefore is a result of and represents a cellular oxidative stress. A cell that experiences oxidative stress may result in cellular components that undergo oxidative modification at thiols (RSH). As RSSH is oxidized with respect to RSH, its formation from RSH will also be more prevalent under cellular oxidative stress conditions. RSSH species, in particular, are potent one-electron reductants that are capable of quenching free radical chemistry that would otherwise be very destructive toward biological membranes. Sulfane sulfur species such as hydropersulfides and polysulfides are known to have antioxidative properties. Thus, it was proposed that RSSH levels may correlate with increased oxidative stress and ferroptosis.