Pyroptosis: Molecular mechanisms and function

Pyroptosis is a lytic form of cell death that is highly regulated and executed by certain members of the Gasdermin protein family. The lytic process occurs because the N-terminal domains of gasdermins possess pore-forming capabilities, thereby leading to cellular swelling and plasma membrane rupture. This process is characterized by membrane pore formation – mediated by caspase-cleaved gasdermins—followed by cell lysis and the release of pro-inflammatory mediators. Depending on the nature of stimuli, different inflammasomes and caspases are activated, leading to pyroptosis via two main mechanisms: the caspase-1-dependent canonical pathway and caspase-1-independent non-canonical pathway. In this review, we first summarize the current understanding of pyroptosis, including its underlying mechanisms and the diverse stimuli that trigger it. We then highlight recent findings related to altered signaling pathways and regulatory mechanisms. Finally, we discuss emerging perspectives and its implications, aiming to deepen insight into this form of cell death and stimulate new avenues for research.