Here, using U87MG astrocytoma cells as well as SH-SY5Y neuroblastoma cells, we showed that CQ, Tat, and gp120 (1) de-acidified endolysosomes, (2) decreased endolysosome numbers and increased endolysosome sizes, (3) increased the number of mitochondria, autophagosomes, fused autophagosomes–endolysosomes, and mitochondrial fragments within autophagosomes and endolysosomes, and (4) increased cell death, effects that were all blocked by the endocytosed iron chelator deferoxamine (DFO). The gene discussed is TAT; the disease is neuroblastoma.