Metamorphosis and development of malaria parasites in the liver are regulated by unconventional autophagy.

Abstract

Malaria parasites encounter diverse conditions as they transition between mosquito and mammalian hosts. A characteristic of the sporozoite stage of the parasite is that once it enters the hepatocyte, it changes its morphology and metabolism. Motile-elongated sporozoites transform into round trophozoites, discard unnecessary organelles, undergo extensive replication, and mature into hepatic merozoites. However, the mechanisms of superfluous organelle elimination and apicoplast biogenesis are unclear. In our latest study, using a conditional mutagenesis system, we clarified the role of Atg7 during parasite metamorphosis in the liver. We found that cytosolic Atg7 is essential for the localization of Atg8 on the membrane and the development of parasites in the blood and liver stages. Parasites lacking Atg7 fail to lipidate Atg8 on the membrane, which leads to impaired exocytosis of micronemes, and parasites eventually fail to mature into hepatic merozoites. This work provides insights into the essential role of Atg7 in maintaining parasite cellular homeostasis during liver stage development.