Role of BH3-only proteins in ER stress and heart failure

Cells may die by a number of mechanisms, whether it be to the detriment or benefit of the organism. This can be external to the control of the cell, or initiated and executed by the cell itself, in response to various stimuli. Programmed cell death, when the cell regulates its own demise in response to specific stimuli, may occur through processes such as apoptosis, necroptosis and pyroptosis (D'Arcy, 2019). The most commonly investigated form of programmed cell death to date is apoptosis, which was first described in 1972 (Kerr et al., 1972). Further advances have been made in the understanding of apoptosis since then, stemming from investigation of programmed cell death in C. elegans (Horvitz, 1999). Its evolutionary conservation as a mechanism of cell death across diverse species, ranging from the aforementioned nematodes to mammals, indicates the ironic importance of this process in the maintenance of life (Severin et al., 2008). Apoptosis is important in both health and disease, regulating embryonic development and displaying polarising roles in pathologies such as cancer and sepsis (Glab et al., 2017b). As such, apoptosis can be both harmful and beneficial to an organism. Additionally, unlike sporadic cell death mechanisms like necrosis, the orderly manner of apoptotic cell disassembly enables the process to go largely undetected by the immune system and avoid initiating inflammatory responses that may otherwise damage the surrounding tissue (Rock and Kono, 2008). Apoptosis can be initiated in response to a variety of stimuli, both intra- and extracellular in origin (Danial and Korsmeyer, 2004). These then activate one of two distinct pathways, ultimately converging on the death of the cell