Apoptosis can be defined as 'gene-directed cellular self-destruction'; it is sometimes referred to as 'programmed cell death' or Type I PCD, although this is really a phenomenon where cells are programmed to die at a particular point, e.g. during embryonic development, and even here cells may go through an apoptotic pathway. However, 'classic' apoptosis is certainly a distinct process from other forms of oncosis leading to necrosis. The new term 'Cell Necrobiology' is an encompassing term for all modes of cell and can be defined as "various modes of cell death: the biological changes, which predisose, precede and accompany cell death; as well as the consequences and tissue response to cell death". The term necrobiology thus includes all the many forms of apoptosis besides 'classic' PCD, including caspase independent apoptosis-like PCD, autophagy or Type II PCD, mitotic catastrophe, necrosis-like PCD, necrosis or oncosis defined as accidental cell death and cell senescence.

Apoptosis can be activated by the 'extrinsic pathway' which is mediated via the Cell Death Receptor pathway. This pathway is typically activated by TNF binding to the receptor, see model of the extrinsic and intrinsic pathways below:-

The 'Intrinsic pathway' can be drug induced, UV-B irradiation, g-irradiation, and reactive oxygen and is mediated via mitochondrial responses to such cellular insults, see model below:-

Classic apoptotic cells can be recognized by a characteristic pattern of morphological, biochemical and molecular changes, which may be broadly and chronologically defined as:

Morphological Changes

• Cell shrinkage
• Cell shape change
• Condensation of cytoplasm
• Nuclear envelope changes
• Nuclear fragmentation
• Loss of cell surface structures
• Apoptotic bodies
• Cell detachment
• Phagocytosis of remains

Functional/Biochemical Changes

• Free calcium ion rise
• bcl2/BAX interaction
• Cell dehydration
• Loss of mitochondrial membrane potential
• Proteolysis
• Phosphatidylserine externalisation
• Formation of Mitochondrial Permeability Transition Pore
• Lamin B proteolysis
• DNA denaturation
• 50-300kb cleavage
• Intranucleosomal cleavage
• Protein cross-linking

Many of these changes may be measured by flow cytometry and some are described below.