The Role of Autophagy and Pyroptosis in Liver Disorders

Abstract

Pyroptosis is a programmed cell death caused by inflammasomes, which can detect cell cytosolic contamination or disturbance. In pyroptosis, caspase-1 or caspase-11/4/5 is activated, cleaving gasdermin D to separate its N-terminal pore-forming domain (PFD). The oligomerization of PFD forms macropores in the membrane, resulting in swelling and membrane rupture. According to the different mechanisms, pyroptosis can be divided into three types: canonical pathway-mediated pyroptosis, non-canonical pathway-mediated pyroptosis, and caspase-3-induced pyroptosis. Pyroptosis has been reported to play an important role in many tissues and organs, including the liver. Autophagy is a highly conserved process of the eukaryotic cell cycle. It plays an important role in cell survival and maintenance by degrading organelles, proteins and macromolecules in the cytoplasm. Therefore, the dysfunction of this process is involved in a variety of pathological processes. In recent years, autophagy and pyroptosis and their interactions have been proven to play an important role in various physiological and pathological processes, and have gradually attracted more and more attention to become a research hotspot. Therefore, this review summarized the role of autophagy and pyroptosis in liver disorders, and analyzed the related mechanism to provide a basis for future research.

The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury

“…After that, water flows into cells due to the osmotic pressure to cause cell swelling. IL-1β and IL-18 then come out through GSDMD pores, leading to inflammation [ 7 ]. Similar to caspase-1, in non-canonical pyroptosis pathways, the activated caspase-4/5/11 cleaves GSDMD into N-GSDMD, which is transferred to the cell membrane and forms plasma membrane pores.…”

“…Moreover, GSDMD is cleaved by caspase-4/5/11, which also leads to K + outflow to activate NLRP3 inflammasome, leading to inflammation [ 22 ]. In caspase-3-mediated pyroptosis pathway, caspase-3 cleaves GSDME and promotes the binding of GSDME-N domain to the cell membrane, thus inducing the formation of cell pores to lead to pyroptosis ( Figure 1 ) [ 7 , 19 , 23 , 24 ]. More and more evidence shows that pyroptosis is involved in many diseases, including I/R injury [ 25 , 26 , 27 ].…”

“…Microautophagy mainly degrades cell components through embedding or dividing cytoplasm on lysosomal membrane. Chaperone-mediated autophagy is a kind of selective autophagy, in which intracellular proteins bound to chaperones are transferred to lysosomes for degradation ( Figure 2 ) [ 7 , 31 ]. Under physiological conditions, autophagy is maintained at the basic level.…”

“…In the above study, autophagy inhibits pyroptosis by suppressing caspase-4. In addition to caspase-4-mediated pyroptosis, there are also caspase-1 and caspase-3-mediated pyroptosis [ 7 ]. Therefore, whether beclin1 overexpression can inhibit the latter two types of pyroptosis in CMECs with H/R is worth studying in the future.…”

“…The formation of pores in cell membrane, cell lysis, and release of proinflammatory cytokines are the characteristics of pyroptosis [ 4 , 5 , 6 ]. Increasing evidence indicates that pyroptosis is involved in many diseases; however, the relevant mechanisms have not been fully understood [ 7 ]. Autophagy is an evolutionarily conserved lysosome-dependent catabolic process, in which cytoplasmic components, including protein aggregates, damaged organelles, and lipid droplets, are degraded, and their components are recovered.…”