In striking contrast with accidental cell death (ACD)-the instantaneous and catastrophic demise of cells exposed to severe insults of physical (e.g., high pressures, temperatures, or osmotic forces), chemical (e.g., extreme pH variations), or mechanical (e.g., shear forces) nature-RCD relies on a dedicated molecular machinery, implying that it can be modulated (i.e., delayed or accelerated) by pharmacological or genetic interventions. Intriguingly, regulated cell death (RCD) is not unique to multicellular life forms, a setting in which RCD has an obvious advantage for organismal homeostasis in both physiological and pathological settings, but is also found (in simplified variants) among unicellular eukaryotes living (at least for part of their life cycle) in colonies (such as several yeast species and Dictyostelium discoideum), and at least in some prokaryotes (e.g., Escherichia coli). A large body of experimental evidence accumulating over the past decades, however, has unveiled and characterized in ever greater detail a set of genetically encoded mechanisms for targeted elimination of superfluous, irreversibly damaged, and/or potentially harmful cells.
The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.įor a long time, cell death has been dismissed by biologists as an inevitable and, hence, spurious consequence of cellular life.
As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives.
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