Skip to main content
. 2024 May 17;13(10):863. doi: 10.3390/cells13100863

Figure 2.

Figure 2

The intersection of apoptosis and pyroptosis is regulated by mitochondria. a. Exogenous apoptosis pathway: ligand/Death receptor/FADD/Pro-caspase-8 binds at the plasma membrane and mediates apoptosis through the downstream Caspase 8/CASP3/PARP pathway; b. Endogenous apoptosis pathway: under the stimulation of endogenous factors such as DNA damage/ER stress/metabolic stress, mitochondria undergo MOMP through the mitochondrial pro-apoptotic proteins BAX/BAK/BAD, and then apoptosis is mediated through the downstream cytochrome C/apaf-1/Caspase 9/Caspase 3/PARP pathway; c. Classical pyroptosis pathway: upon PAMP/DAMP stimulation, NLRP3/ASC/Pro-caspase-1 forms pyroptosis vesicles, which mediate pyroptosis via active Caspase 1 to activate Pro-IL-1/Pro-IL-18 and cleave GSDMD; d. Non-classical pyroptosis pathway: the presence of intracellular LPS contributes to the occurrence of Caspase 4/11/GSDMD-associated pyroptosis; e. Intersecting pathways of apoptosis/pyroptosis regulated by mitochondria: elevated intracellular Iron causes mitochondria to mediate the onset of pyroptosis via the elevated ROS/Tom20 oligomerization/BAX/MOMP/cytochrome C release/apaf-1/Caspase 9/Caspase 3/GSDME pathways. Caspase 1 in pyroptosis vesicles can mediate pyroptosis via the mitochondrial pro-apoptotic protein t BID/apaf-1/Caspase 9/Caspase 3/GSDME pathway. High expression of HK-II inhibits both the pathway of cells toward cytochrome C/apaf-1/Caspase 9/Caspase 3/PARP-associated pyroptosis and the pathway of cells toward the cytochrome C/apaf-1/Caspase 9/Caspase 3/GSDME-associated pyroptosis pathway, and Triptolide inhibits the expression of HK-II. Inactivation of mitochondrial anti-apoptotic proteins such as Mcl-1 and Bcl-xL instead led to mitochondrial-mediated pyroptosis via the MOMP/cytochrome C release/apaf-1/Caspase 9/Caspase 3/GSDME pathway. Bcl-2 can inhibit pyroptosis by interacting with Caspase 1, which enhances GSDMD cleavage at the D87 site. In the presence of high bile acid levels, LND, and ANT1, mitochondria mediate pyroptosis via MPT/cytochrome C/Apaf-1/Caspase 4/Caspase 3/GSMDE.