The survival or death of individual cells is paramount to a myriad of biological processes in metazoans. Although it is thought that some cells die “accidently” in a nonprogrammed manner, many biological processes depend on orchestrated processes of cell death, collectively called “regulated cell death.” This collection of cell death processes imparts consequences not only on the dying cell but also on the surrounding cells and tissues. Current work has not only described this compendium of cell death processes in detail but has also identified scenarios in which cell death is not actually the end of cellular activities. For example, evidence indicates that in the case of infection, the pathogen can survive after the cell has died. This chapter discusses some of the ways by which cells die in a regulated manner and the downstream consequences of these death processes.
Acronyms and Abbreviations
Atg, autophagy-related gene; Bcl-2, B-cell lymphoma 2; BIRs, baculovirus internal repeats; DAMPs, damage associated molecular patterns; dsRNA, double-stranded RNA; ER, endoplasmic reticulum; GPX4, glutathione peroxidase 4; IAP, inhibitor of apoptosis protein; ICD, immunogenic cell death; IL, interleukin; LPS, lipopolysaccharide; MDM2, mouse double minute 2; miRNA, microRNA; MLKL, mixed lineage kinase domain-like pseudokinase; MOMP, mitochondrial outer membrane permeabilization; MTP, mitochondrial permeability transition; NETs, neutrophil extracellular traps; NHL, non-Hodgkin's lymphoma; PAMPs, pathogen associated molecular patterns; PARP, poly-ADP ribosyl polymerase; PITs, pore-induced intracellular traps; PUFA, polyunsaturated fatty acid; RCD, regulated cell death; RIPK, receptor-interacting protein kinase; ROS, reactive oxygen species; TfR1, transferrin receptor 1; TLR, toll-like receptor; TNF, tumor necrosis factor;
Cell numbers are governed by cell division, which determines the rate of cell production, and cell death, which dictates the rate of cell loss. To control this process, several forms of programmed, or regulated, cell death (RCD) exist that control cell turnover. Alterations in the expression or function of the genes that control RCD can upset this balance, contributing to or causing disease. RCD is crucial for clearing senescent or defective cells as well as those infected with pathogens, yet excess cell death or inadequate strategies to process cell debris can lead to immunodeficiencies. Twelve forms of programmed cell death are recognized by the Nomenclature Committee on Cell Death (Table 14–1),1 and many existing therapeutics aim to target one or more RCD pathways. Cross-talk between the regulatory pathways that govern the different forms of RCD, as well as heterogeneity in the susceptibility to and execution of RCD add complexity to the organism’s ability to regulate cell numbers, further emphasizing the importance of this process.
TABLE 14–1.Forms of Regulated Cell Death ||Download (.pdf) TABLE 14–1. Forms of Regulated Cell Death
Cell Death Form
Form of RCD triggered by extracellular perturbations, propagated by caspase-8, and executed by caspase-3
1, 49, 124
Form of RCD triggered by intracellular perturbations characterized by mitochondrial outer membrane ...