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Current concepts in apoptosis: The physiological suicide program revisited


Apoptosis, or programmed cell death (PCD), involves a complex network of biochemical pathways that normally ensure a homeostatic balance between cellular proliferation and turnover in nearly all tissues. Apoptosis is essential for the body, as its deregulation can lead to several diseases. It plays a major role in a variety of physiological events, including embryonic development, tissue renewal, hormone-induced tissue atrophy, removal of inflammatory cells, and the evolution of granulation tissue into scar tissue. It also has an essential role in wound repair. The various cellular and biochemical mechanisms involved in apoptosis are not fully understood. However, there are two major pathways, the extrinsic pathway (receptor-mediated apoptotic pathway) and the intrinsic pathway (mitochondria-mediated apoptotic pathway), which are both well established. The key component in both is the activation of the caspase cascade. Caspases belong to the family of proteases that ultimately, by cleaving a set of proteins, cause disassembly of the cell. Although the caspase-mediated proteolytic cascade represents a central point in the apoptotic response, its initiation is tightly regulated by a variety of other factors. Among them, Bcl-2 family proteins, TNF and p53 play pivotal roles in the regulation of caspase activation and in the regulation of apoptosis. This review summarizes the established concepts in apoptosis as a physiological cell suicide program, highlighting the recent and significant advances in its study.



apoptosis protease activating factor-1


B-cell lymphoma family


Bcl-2 homology


truncated Bid


baculoviral IAP repeat


BIR repeat-containing ubiquitin-conjugating enzyme


caspase recruitment domain


cysteine-rich extracellular domain


death-inducing signaling complex


death domain


death effector domain


death-inducing receptor


endoplasmic reticulum


Fas-associated death domain protein


FADD-like-ICE-inhibitory protein or FLICE inhibitory protein




inhibitor of apoptosis




mitochondrial outer membrane permeabilization


programmed cell death


p53-up-regulated modulator of apoptosis




permeability transition pore


receptor interacting protein


TNF alpha-converting enzyme


transforming growth factor-β


tumor necrosis factor α


tumor necrosis factor receptor-1


TNF-related apoptosis-inducing ligand


TNF-receptor associated protein with death domain


terminal deoxynucleotidyl transferase-mediated (TdT-mediated) dUTP-digoxigenin nick end labeling


voltage-dependent anion channel


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Correspondence to Ganapathy K. Bhat.

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Chowdhury, I., Tharakan, B. & Bhat, G.K. Current concepts in apoptosis: The physiological suicide program revisited. Cell Mol Biol Lett 11, 506–525 (2006).

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Key words

  • Apoptosis
  • Programmed cell death
  • Pathways
  • Caspases
  • Bcl-2
  • p53
  • TNF
  • Apaf