The role of the apoptosome in the activation of procaspase-9

Apoptosis, also called programmed cell death, is a physiological process that causes a number of morphological and biochemical changes, occurring in the cell and leading to its death. Along with the processes of proliferation, differentiation and maturation, it is responsible for controlling the amount and types of cells, removing those that are unnecessary or dangerous for the organism. The most important enzymes involved in apoptosis are caspases, which hydrolyze the structural and functional proteins, ultimately leading to cell death. The caspases are synthesized in the cell as inactive zymogens and have to be activated in order to perform their functions. Two pathways lead to the activation of caspases: the extrinsic pathway associated with membrane receptors and their ligands, and the intrinsic pathway dependent on mitochondria. The central element in the mitochondrial pathway is a special protein complex, the apoptosome, which enables and facilitates the activation of procaspase 9. Apaf-1, cytochrome c and dATP/ATP are needed to form the apoptosome. Active apoptosomes arise only in response to apoptotic agents. There are many factors regulating apoptosome formation in physiological conditions. It was shown that disorders in apoptosome formation have great importance in the pathogenesis of cancer and the occurrence of resistance to chemotherapy. Therefore, research continues on finding compounds which are able to induce or inhibit the formation of the apoptosome. The results of this research will have great importance for the treatment of cancers or diseases resulting from an excessively prolonged process of apoptosis. In this paper the general characteristics of the apoptosome, its role and mechanism of formation are presented. Additional information is given on the regulation of its activity and on the role of disturbance of apoptosome activity in cancerogenesis and chemoresistance. Particular attention is paid to those compounds that are able to influence the formation and activation of the apoptosome, and may in future be interesting therapeutic tools.