Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in Toxoplasma gondii

摘要: Autophagy is a catabolic process widely conserved among eukaryotes that permits the rapid degradation of un- wanted proteins and organelles through lysosomal pathway. This mechanism involves formation double-membrane structure called autophagosome sequesters cellular components to be degraded. To orchestrate this process, yeasts animals rely on set autophagy-related (ATGs). Key these factors ATG8, cytoplasmic protein recruited nascent autophagosomal membranes upon induction autophagy. Toxoplasma gondii potentially harmful human pathogen in which only subset ATGs appears present. Although eukaryotic parasite seems able generate autophagosomes stresses such as nutrient starvation, full functionality biological relevance canonical autophagy pathway are yet unclear. Intriguingly, T. gondii, ATG8 localizes apicoplast under normal intracellular growth conditions. The nonphotosynthetic plastid enclosed by four resulting from secondary endo- symbiosis. Using superresolution microscopy biochemical techniques, we show TgATG8 outermost membrane organelle. We investigated unusual function at generating conditional knockdown mutant. Depletion led loss organelle subsequent replication defects, in- dicating essential for maintaining homeostasis thus survival tachyzoite stage. More precisely, abnormal segregation into progeny because physical interactions with centrosomes. IMPORTANCE By definition, leads digestion recycling components. molecular machinery was identified mainly model organisms but remains poorly characterized phylogenetically distant apicomplexan parasites. have uncovered an gondii: crucial inside its host cell. Seemingly unrelated associates outer non- photosynthetic harbored apicoplast, there it plays important role centrosome-driven inheritance during cell division. not reveals unexpected also sheds new light division vital group impor- tant animal pathogens.