Fig. 5

Ferroptosis and significant transition metals overview. In this figure we summarise an overview of main roles of various transition metals in ferroptosis documented in this review. Iron (Fe) generates hydroxyl radicals by undergoing the Fenton reaction. The iron pool is supplemented by NCOA4 mediated ferritinophagy or by iron import through transferrin receptor 1. Zinc (Zn) is found in abundant superoxide dismutase (Cu/Zn-SOD) and in metallothionein (MT). Cu/Zn-SOD scavenges superoxide and MT has a pro-antioxidant effect. Zinc is further present in lipoxygenase (LOX) generating PUFAS-OOH. Selenium (Se) acts as a ferroptosis suppressor mainly by the presence in GPX4. Copper (Cu) is found in Cu/Zn-SOD and MT. Ceruloplasmin (Cp) has a key role in the maintenance of Fe²⁺and Fe³⁺pool balance. Cu was also found to induce an autophagic degradation of GPX4. Molybdenum (Mo) participates in the form of molybdenum sulphate (MoB) on the catalytic generation of superoxide radical. Cobalt (Co) undergoes Fenton-like reaction generating ROS. Nickel (Ni) dysregulates iron homeostasis decreases expression of GPX4. Platinum (Pt) is represented by the platinum derived chemotherapeutics – cis-platin (Cis-Pt) and its derivate Platin B (Pt-B). Cis-platin alone increases expression of transferrin receptor 1 and inhibits GPX4. 4-carboxylphenylboronic acid added in Platin B is potent GSH scavenger which depletes GPX4 from its crucial substrate. Cadmium (Cd) activates Heme oxygenase 1 (HMOX1), inactivates MT and various antioxidants and induces ER stress mediated ferritinophagy. Mercury (Hg) decreases the expression of GPX4. CH3HgCl also directly binds to the selenol group (-SeH) of GPX4 inhibiting its activity. Lead (Pb) decreases expression of GPX4 and SLC7A11 transport system. Uranium (U) dysregulates iron homeostasis and by γ-radiation generates ROS and alters expression of SLC3A2. All the pathways are mentioned in the following summarising Table 1