Cell biology of inflammasome activation. Issue 11 (November 2021)

• Record Type: Journal Article
• Authors: Pandey, Abhimanu; Shen, Cheng; Feng, Shouya; Man, Si Ming
• Is Part Of: Trends in cell biology. Volume 31:Issue 11(2021)
• Page Start: 924
• Page End: 939
• Publication Date: 2021-11
• Subjects: caspase -- cell death -- IL-1 -- IL-18 -- inflammasome -- microtubule-organizing center; Cytology -- Periodicals; Cytology -- Research -- Periodicals; 571.6
• DOI: 10.1016/j.tcb.2021.06.010
• Languages: English
• ISSNs: 0962-8924

Abstract

Abstract : Organelles are critical structures in mediating the assembly and activation of inflammasomes in mammalian cells, resulting in inflammation and cell death. Assembly of inflammasomes can occur at the mitochondria, endoplasmic reticulum, nucleus, trans-Golgi network, or pathogen surface, facilitated by the overarching architecture of the cytoskeleton. NLRP3 and Pyrin inflammasome sensors may form smaller speckles and converge on a single larger speck at the microtubule-organizing center (MTOC). This signaling hub activates multiple mammalian inflammatory and apoptotic caspases, cytokine substrates, the pore-forming protein gasdermin D, and the plasma membrane rupture protein ninjurin-1 (NINJ1), allowing pyroptosis, cellular disintegration, and inflammation to ensue. In this review, we highlight the role of mammalian cell types and organellar architectures in executing inflammasome responses. Highlights: Inflammasome components are expressed in immune and nonimmune cells, contributing to sensing of pathogens and danger signals, triggering inflammation and cell death, and shaping the development of infectious diseases, autoimmunity, cancer, and metabolic diseases. Inflammasome sensors trigger inflammasome-dependent and/or inflammasome-independent functions in different mammalian cells. Cellular organelles such as mitochondria, endoplasmic reticulum, Golgi apparatus, nucleus, microtubule-organizing center, and even the pathogen surface, act as platforms for trafficking and assembly of inflammasome complexes. Inflammasome-mediated, gasdermin-D-dependent, pyroptotic cell death is an active cellular process, requiring the plasma membrane disruptor ninjurin-1.