BIO-RAD Overview of Regulated Cell Death

The definition of cell death is the irreversible degeneration of cellular functions resulting in the loss of cellular integrity (Galluzzi et al. 2018). Cell death is a crucial step in organism development, tissue homeostasis, and host defense. There are many mechanisms of regulated cell death (RCD), where signal transduction molecules are not only initiated but also involved in the propagation of cell death. 

Initiation of RCD can result from tissue-turnover, known as programmed cell death (PCD), or disruption of the intercellular or extracellular environment (stress driven RCD). Regulated cell death is involved in immunological processes including elimination of infected cells, removal of effector immune cells, and lymphocyte development. RCD, which can act independently of or as a component of homeostasis, eliminates cells that no longer have a purpose and/or that are potentially dangerous. Here damage-associated molecular patterns (DAMPs) and alarmins are released by damaged cells to signal their potential hazard.

Pattern recognition receptors (PRRs) are involved in the protection against invading pathogens, and are activated either by recognizing PAMPs or DAMPs. This engagement not only induces an inflammatory response but instigates three Regulated Cell Death pathways: apoptosis, necroptosis, and pyroptosis. Read our overview on PPR to learn more about these receptors that identify and respond to infection or read about which specific cell death mechanisms are induced and the markers involved that can be used to identify this process.

Accidental cell death (ACD), the instantaneous form of cell death caused by physical, chemical, or mechanical means, and leading to disassembly of the plasma membrane and cellular senescence, the irreversible loss of proliferative potential associated with specific morphological and biochemical features, are not forms of regulated cell death.

The area of RCD continues to develop and advance, with the discovery of new mechanisms. The definitions of the most commonly found are described here.