[Mitochondria and cell death]

Abstract

In living cells, apoptosis is effected through many different pathways. Programmed cell death (PCD) may proceed with the involvement of membrane receptors, mitochondria, granzyme B, or the endoplasmic reticulum. The mitochondrial pathway is initiated from within the cell as a consequence of changes in reductive potential. It may also be caused by DNA mutation or various disturbances in the cell's metabolism. In some cases, the intrinsic pathway is connected with the extrinsic one, generated by the cell's environment. The central organelle which initiates the intrinsic pathway is the mitochondrion. Changes in the permeability of the mitochondrial outer membrane cause an outflow of cytochrom c, which interacts with cytoplasmic factor Apaf-1 and procaspase 9, in the presence of ATP, and thus triggers the caspase cascade. Apart from cytochrom c, more than 40 regular or executor particles involved in apoptosis might be released from the mitochondrion. These include Smac/DIABLO, Omi/HTR A2, endonuclease G, AIF, and IAP. Moreover, regulatory functions are performed by Bcl-2 family proteins present in the cytoplasm that affect mitochondrial membrane permeability and by heat shock proteins (HSPs), both of these regulating caspase function. The phenomenon of programmed cell death is the main subject of research for many groups of scientists. There are still many aspects which need to be elucidated.