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Corresponding to its importance in cell count homeostasis in the body, apoptosis is a tightly regulated phenomenon. Both extracellular and intracellular molecules provide multiple regulatory and counter-regulatory pathways. Cell death is usually a response to the cell microenvironment, where the absence of certain factors (survival factors) or the presence of lethal factors promotes apoptosis. Surrounding cells, soluble mediators and the extracellular matrix regulate cell death and survival. Surrounding cells can synthesize survival or lethal factors. The intracellular regulation of apoptosis is also one of the forefront fields in biomedicine research. During the past five years, tremendous progress has been made in understanding apoptosis as a result of molecular identification of the key components of this intracellular suicide program. Biochemical activation of these key components of the cell death program is responsible for the morphological changes observed in apoptosis, including mitochondrial damage, nuclear membrane breakdown, DNA fragmentation, chromatin condensation and the formation of apoptotic bodies. Caspase activation plays a central role in the execution of apoptosis. Most caspases are constitutively expressed as inactive proenzymes (procaspases) in the cytosol and according to some reports in the mitohondria. Caspases are sequentially activated by proteolysis during apoptosis. In this review, we focus on the biochemical pathways that control caspase activation, particularly the activation pathways that are initiated by cell surface death receptors and mitochondria.

Apoptosis is evolutionary conserved form of cell suicide. Tumor necrosis factor-alpha (TNF-alpha) or Fas Ligand activated apoptosis by binding of the plasma membrane receptor. The activation of TNF Receptor 1 or Fas-Ligand Receptor lead to activate of caspase 8. The activation of the caspase-8 lead to activate the cell-death machinery cascade. The inhibitor of cell death machinery is Bcl-2 also fails to prevent Bax-induced cytochrome c release, activation of caspase-3, membrane blebbing, nuclear fragmentation, and cell death. Bcl-2 is important cell live-death regulator. Cleavage of specific protein subsets is a key event in the execution of apoptosis. Protein degradation may serve for the structural alterations in the process of cell self-destruction, but it may also function as a switch in the decisions between apoptosis and necrosis or apoptosis and cell proliferation.