One of the most prevalent forms of cell death in the human body is phagoptosis, where one cell kills and engulfs another cell that would otherwise continue living. The mechanism of phagoptosis is poorly understood. We have recently shown that ovarian nurse cells die by this form of cell death, providing a powerful model for phagoptosis. In the Drosophila ovary, there are 15 nurse cells that support the oocyte throughout development. In late stages of oogenesis the nurse cells dump their cytoplasmic contents into the oocyte, and are subsequently acidified and cleared by the surrounding stretch follicle cells. We have previously found that the engulfment machinery (Draper, Ced-12, etc.) acts through the JNK pathway within the stretch follicle cells to promote nurse cell death, but the exact mechanism remained elusive. Through genetic manipulation and live imaging, we have determined that lysosomal components actively kill the nurse cells. To understand the role of lysosomes more precisely, we cultured late stage egg chambers and live-imaged nurse cells throughout death with probes and GFP fusion proteins. LysoTracker staining shows a gradual increase in nurse cell acidification and clearance by surrounding follicle cells. A candidate RNAi screen of genes encoding lysosomal proteins identified several key lysosomal components such as V-ATPases and cathepsins, which are required non-autonomously for the acidification and clearance of nurse cells. Additional hits from the RNAi screen are being followed up by confocal imaging and live imaging of GFP-tagged proteins. Altogether, this work further characterizes this novel form of cell death and illustrates the importance of non-autonomous control over cell death. Our work also demonstrates an essential role for lysosomal machinery in actively killing neighboring cells.