A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C-elegans

Similar to mammalian excitotoxic cell death, necrotic-like cell death (NCD) in Caenorhabditis elegans can be initiated by hyperactive ion channels. He re we investigate the requirements for genes that execute and regulate prog rammed cell death (PCD) in necrotic-like neuronal death caused by a toxic M EG-4 channel. Neither the kinetics of necrosis onset nor the total number o f necrotic corpses generated is altered by any C. elegans mutation known to block PCD, which provides genetic evidence that, the activating mechanisms for NCD and apoptotic cell death are distinct. In contrast, all previously reported ced genes required for phagocytotic removal of apoptotic corpses, as well as ced-12, a new engulfment gene we have identified, are required for efficient elimination of corpses generated by distinct necrosis-inducin g stimuli. Our results show that a common set of genes acts to eliminate ce ll corpses irrespective of the mode of cell death, and provide the first id entification of the C. elegans genes that are required for orderly removal of necrotic cells. As phagocytotic mechanisms seem to be conserved from nem atodes to humans, our findings indicate that injured necrotic cells in high er organisms might also be eliminated before lysis through a controlled pro cess of corpse removal, a hypothesis that has significant therapeutic impli cations.