Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Abstract

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.

USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics

“…1 This process is finely tuned by numerous cellular signaling pathways involving hundreds of pro-apoptotic and anti-apoptotic factors. 2,3 Inhibitor of apoptosis proteins (IAPs) are a conserved protein family containing the baculoviral IAP repeat (BIR) domain.…”

Tousled-like kinase mediated a new type of cell death pathway in Drosophila

“…As a further subtype of RCD, the cell death that occurs in development is referred as programmed cell death (PCD). 1 Although caspase-dependent apoptosis has crucial roles in development, other type(s) of PCD may exist. 2 The Drosophila eye is an elegant model system with which to study PCD in development; 3,4 the patterning of the Drosophila eye is highly stereotypic and well characterized.…”

“…6 Apoptosis is an important variant of PCD and is executed by caspases. 1 In Drosophila, these caspases include Dronc, a main initiator caspase, and DrICE and Dcp-1, which are activated by Dronc. 9 The activities of caspases can be inhibited by two endogenous proteins, DIAP1 and DIAP2.…”

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