Fig. 6

Pyroptosis and significant transition metals overview. In this figure we summarise an overview of main roles of various transition metals in pyroptosis documented in this review. Iron (Fe) generates ROS, which activates ROS-NLRP3-ASC-Caspase-1 or ROS-Tom20-Bax-Caspase-GSDME pathway. Zinc (Zn) contributes to pyroptosis by NLRP3-ASC-Caspase-1 or alleviates it by the TRPC6-NLRP3-ASC-Caspase-1 or ZEB2. Selenium (Se) depletion leads to the increase in free ROS or TXRND3 dysregulation. Se deficiency induces upregulation of miR-1656 leading to heightened expression of pyroptosis associated genes such as NLRP3 by suppressing GPX4 release. Copper (Cu) activates inflammasome by the IRE1α/XBP1(ER stress)-NLRP3 axis. Cobalt (Co) nanoparticles induce the ROS-NLRP3-ASC-Caspase-1 pathway. Cobalt also induces GDSME-Caspase-3/8/9 activation. Nickel (Ni) up-regulates ASC, AIM2, NLRP3, Caspase-1, IL-18 and IL-1β. Platinum (Pt) is represented by the most used platinum derived chemotherapeutics – cis-platin (Cis-Pt) and its derivate lobaplatin (Lob-Pt). Cis-Pt induces the CAPN1/CAPN2-BAK/BAX-Caspase-9-Caspase-3-GSDME pathway. Cis-Pt also activates the MEG3-NLRP3-Caspase-1-GSDMD axis. Cis-Pt inhibits Caspase-3-GSDMD pathway in non-cancerous cells. Lobaplatin activates Caspase-3-GSDME pathway. Cadmium (Cd) activates both ROS-NLRP3-Caspase-1 and IRE1α/XBP1(ER stress)-NLRP3 pathways. Lead (Pb) increases NLRP3 and Caspase-1 expression. Mercury (Hg) disrupts ROS production and inhibits the ASC pyroptosome and GDSMD cleavage. Lead (Pb) increases NLRP3 expression and Caspase-1. Molybdenum (Mo) role in pyroptosis is unclear and therefore we didn´t visualised its role in the scheme. Uranium (U) role in pyroptosis wasn´t yet documented. All the pathways are mentioned in the following summarising Table 1