Abstract

FERNANDEZ-LAZARO, Diego; SANZ, Begoña  and  SECO-CALVO, Jesús. Mechanisms of programmed cell death: structural and functional pathways. A narrative review. Invest. clín [online]. 2024, vol.65, n.2, pp.230-252.  Epub June 06, 2024. ISSN 0535-5133.  https://doi.org/10.54817/ic.v65n2a09.

Apoptosis, necroptosis, and autophagy are cellular mechanisms by which cells are programmed to die under various physiological and developmental stimuli. A multitude of protein mediators of programmed cell death have been identified, and apoptosis, necroptosis, and autophagy signals have been found to utilize common pathways that elucidate the proteins involved. This narrative review focuses on caspase-dependent and caspase-independent programmed cell death systems. Including studies of caspase-dependent programmed cell death, extrinsic pathway apoptotic mechanisms, phosphatidylserine (PS), FAS (APO-1/CD95), tumor necrosis factor (TNF) receptor type 1 (TNF-R1) and TNF-related apoptosis-inducing ligand (TRAIL), and intrinsic or mitochondrial pathway such as cytochrome C, the Bcl-2 family of proteins and Smac/Diablo. The Bcl-2 family has apoptotic mediators Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), Bcl-2-interacting protein BIM (Bim), Bcl-2 agonist of cell death (Bad), Bid, Bcl-2 adenovirus E1B 19kDa-interacting protein 1 NIP3 (Bnip3), BMF, HRK, Noxa and PUMA and antiapoptotic proteins such as Bcl-2 itself, Mcl-1, Bcl-w, A1, and Bcl-XL. Moreover, caspase-independent programmed cell death pathways include the mitochondrial pathway with the protein mediators apoptosis inducing factor (AIF) and endonuclease G, and the pathways necroptosis, and autophagy. Understanding programmed cell death from those reported in this review could shed substantial light on the processes of biological homeostasis. In addition, identifying specific proteins involved in these processes is mandatory to identify molecular biomarkers and therapeutic targets. Furthermore, it could provide the ability to modulate the programmed cell death response and could lead to new therapeutic interventions in a disease.

Keywords : apoptosis; caspases; mitochondrial/intrinsic pathway; extrinsic pathway; necroptosis; autophagy.

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