Pathogen-induced formation of a nascent organelle derived from mitochondria

Abstract

Intracellular pathogens extensively remodel host cells to create environments that support their survival and replication. How pathogens manipulate host organelle biology to promote infection remains a central question in microbial pathogenesis. Here we show that the human parasite Toxoplasma gondii induces the biogenesis of acidified compartments derived from host mitochondria that promote parasite growth. Following infection, host mitochondria shed large structures positive for outer mitochondrial membrane (OMM), termed SPOTs. SPOTs matured into multivesicular compartments that engulfed cytosolic protein and functional lysosomes. The acquisition of host lysosomes by SPOTs required host ESCRT machinery and the parasite effector TgGRA7, and drove the acidification of the SPOT lumen. Disrupting SPOT acidification impaired parasite proliferation, implicating SPOT maturation in parasite fitness. These findings show that an intracellular pathogen co-opts host machinery to drive the formation of a nascent organelle derived from mitochondria, and raise the possibility that mitochondria can be reprogrammed to generate new organelles with specialized functions. One-Sentence SummaryAn intracellular pathogen hijacks host mitochondrial membranes and ESCRT machinery to generate an acidified organelle that supports parasite replication.