Regulated cell death is a vital and dynamic process in multicellular organisms that maintains tissue homeostasis and eliminates potentially dangerous cells. Apoptosis, one of the better-known forms of regulated cell death, is activated when cell-surface death receptors like Fas are engaged by their ligands (the extrinsic pathway) or when BCL-2-family pro-apoptotic proteins cause the permeabilization of the mitochondrial outer membrane (the intrinsic pathway). Both the intrinsic and extrinsic pathways of apoptosis lead to the activation of a family of proteases, the caspases, which are responsible for the final cell demise in the so-called execution phase of apoptosis. In this review, I will first discuss the most common types of regulated cell death on a morphological basis. I will then consider in detail the molecular pathways of intrinsic and extrinsic apoptosis, discussing how they are activated in response to specific stimuli and are sometimes overlapping. In-depth knowledge of the cellular mechanisms of apoptosis is becoming more and more important not only in the field of cellular and molecular biology but also for its translational potential in several pathologies, including neurodegeneration and cancer.
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February 2022
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Cover Image
Cover Image
Immunofluorescence staining of WT, IKKα KO, IKKβ KO and IKKα/β DKO HCT116 cells with anti-p65 NF-kB antibody (green); nuclei stained with DAPI (blue) by Jack Prescott. This figure demonstrates a critical role for IKKα in TNFα-induced p65 nuclear translocation with only a minor role for IKKβ.
Review Article|
February 11 2022
The concept of intrinsic versus extrinsic apoptosis
In Collection
Cell death and survival
Laura Lossi
Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, I-10095 Grugliasco, Torino, Italy
Correspondence: Laura Lossi (laura.lossi@unito.it)
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Publisher: Portland Press Ltd
Received:
December 22 2021
Revision Received:
January 20 2022
Accepted:
January 21 2022
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem J (2022) 479 (3): 357–384.
Article history
Received:
December 22 2021
Revision Received:
January 20 2022
Accepted:
January 21 2022
Citation
Laura Lossi; The concept of intrinsic versus extrinsic apoptosis. Biochem J 11 February 2022; 479 (3): 357–384. doi: https://doi.org/10.1042/BCJ20210854
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