Apoptosis: the fly point of view

International audienceIt is now established that genes involved in the execution of programmed cell death by apoptosis are relatively well conserved throughout evolution. However, the control of commitment to apoptosis exhibits some differences between organisms. In C. elegans, genetic studies have led to the identification of the ced genes (cell death) ced-3 and ced-4 that are essential to trigger cell death, and ced-9 that antagonizes the activities of ced-3 and ced-4. CED-3 is a caspase (cysteinyl aspartase) and CED-9 is homologous to proteins of the Bcl 2 family. In mammals, two main pathways of apoptosis have been identified. The intrinsic pathway is regulated by the bcl 2 family genes (the homologs of CED 9) but is more complex than in C. elegans and most data suggest that this family controls caspase activation by regulating mitochondrial membrane permeability and the release in the cytoplasm of proapoptotic factors including cytochrome c, which participate in caspases activation. An extrinsic pathway, which is activated by the binding of ligands on death receptors, activates in some cases caspases in a Bcl 2 independent fashion. In Drosophila the way of action of of Bcl 2 homologs is probably different. No release of mitochondrial proteins during Drosophila cell death has been demonstrated. Instead, numerous actors involved in the cell death process migrate from cytoplasm to mitochondria. Furthermore, although numerous homologs of actors of the extrinsic pathway exist in Drosophila, the signaling cascade seems quite different.On the other hand, the genetic approach performed in Drosophila has resulted in the discovery of new apoptosis regulators encoded by genes located on the 75C region of the third chromosome. The products of these genes (RPR, HID, GRIM and SICKLE) act through binding to IAPs (Inhibitor of Apoptosis Proteins), disrupting inhibition of caspases managed by IAP. Their action on IAPs is similar to that of mammalian Smac/Diablo and Omi/HtrA2 but, unlike these, RPR, HID, GRIM and SICKLE act upstream or independently of mitochondria. More recently, genetic and genomic tools available in Drosophila have also allowed discovering micro RNA (Bantam and mir 14) that regulates apoptosis.Finally, homologs of various oncogenes and tumor suppressor genes which control apoptosis have also been identified in Drosophila. In this paper, we review the regulation of apoptosis in Drosophila, and we discuss the extent to which the data obtained in this organism can be helpful to understand apoptosis in other species