Many factors can cause cells to undergo apoptosis. However, the discovery that shared morphological and biochemical changes occurred independently of the apoptotic triggering event led to postulate that most apoptotic pathways converge on a small number of common effectors, see, e.g. (Elmore, 2007; Galluzzi et al., 2018). The relative timing of caspase activation and mitochondrial cytochrome c release distinguishes two primary routes. In intrinsic apoptosis, cytochrome c is released from the mitochondrial intermembrane space before caspase activation, whereas in extrinsic apoptosis, an effector caspase is triggered before mitochondrial changes. The activation of intracellular sensors that detect, e.g. DNA damage, the presence of viral infections, or the lack of survival signals provided by other cells is the first stage of the intrinsic pathway. The extrinsic pathway, on the other hand, begins with a pro-death extrinsic signal that involves natural killer or CD8-positive cytotoxic T lymphocytes in the immune system (Yanumula et al., 2021; Losse, 2022).
References
Elmore, S. (2007). Apoptosis: A review of programmed cell death. Toxicologic Pathology, 35(4), 495-516. Elmore, S. (2007) Apoptosis: A review of programmed cell death. Toxicol. Pathol. 35, 495–516 https://doi.org/10.1080/01926230701320337
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., Annicchiarico-Petruzzelli, M., Antonov, A. V., Arama, E., Baehrecke, E. H., Barlev, N. A., Bazan, N. G., Bernassola, F., Bertrand, M. J. M., Bianchi, K.,… Kroemer, G. (2018). Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death & Differentiation, 25(3), 486-541. https://doi.org/10.1038/s41418-017-0012-4
Lossi, L. (2022). The concept of intrinsic versus extrinsic apoptosis. Biochemical Journal, 479(3), 357-384. https://doi.org/10.1042/BCJ20210854
Yanumula, A., and & Cusick, J. K. (2021). ; Biochemistry, extrinsic pathway of apoptosis. In StatPearls, StatPearls Publishing. Copyright © 2021, StatPearls Publishing LLC, Treasure Island, FL
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