The components of the cell death pathways are conserved in Drosophila and mammals. The RHG proteins Reaper (Rpr), Hid, Grim, Sickle, HtrA2/Omi and Jafrac2 are upstream pro-apoptotic proteins. They are regulated by death or survival signals. For instance, Ras/MAPK signaling negatively regulates the activity of Hid. Upon cell death signals, the RHG proteins release the initiator caspase Dronc from inhibition by Diap1. Released Dronc binds to Ark and forms the apoptosome, which activates the effector caspases Dcp-1 and DrICE, triggering apoptotic processes by cleaving many cellular substrates. In mammals, Smac and HtrA2, released from mitochondria, promote cell death by binding to XIAP and releasing initiator caspases such as Caspase-9. In contrast to Drosophila, apoptosome formation requires cytochrome c release from mitochondria, which binds to Apaf-1 and then recruits Caspase-9 for activation. Thereafter, effector caspases such as Caspase-3 and Caspase-7 are activated to trigger downstream apoptotic reactions.