The Apoptosome: The Executioner of Mitochondria‐mediated Apoptosis

Abstract

The apoptosome is a molecular complex of two major components – the adapter protein apoptotic protease activating factor 1 ( Apaf1 ) and the protease caspase‐9. These are assembled during apoptosis upon Apaf1 interaction with cytochrome c , which is released from the intermembrane space of mitochondria under precise cell death stimuli. Apoptosome assembly triggers effector caspase activation, which – in turn – drives cell demise. Several proteins bind and regulate apoptosome. This complex is found in vertebrates, even though similar functions are played by ortholog proteins through slightly different mechanisms also in lower eukaryotes. Given the involvement of apoptosome dysfunctions in human diseases, this complex is also a relevant molecular target in biomedicine. Key concepts It was a stunning discovery to find out that cytochrome c , essential for adenosine triphosphate (ATP) production and cell life, was involved in a cell death pathway. Apoptosis regulation is essential for avoiding unwanted cell death and allowing the correct development and homoeostasis of the whole organism. Therefore there are several regulators of apoptosome activity. Caspases and Apaf1 have a key phylogenetically conserved role in apoptosis. Apoptosis is evolutionary well‐conserved in terms of its basic mechanisms; however, the role of mitochondria in apoptosis of organisms other than vertebrates needs to be clearly defined.

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“…In the presence of cytochrome c, activating apoptotic protease activating factor-1 (apaf-1), initiates apoptosome complex formation [35,36]. Apoptosome complex then activates Ca 2+ dependent serine proteases of the intrinsic pathway (caspase-9), which activates the downstream signaling cascade and activates caspase-3 leading to programmed cell death [37]. Therefore, the increased percentage of apoptotic cells following AETE treatment in the present study might be due to the activation intrinsic pathway of apoptosis.…”