autophagy-related atg8 localizes to the apicoplast of the human malaria parasite plasmodium falciparumautophagy-related atg8本地化的apicoplast人类恶性疟原虫.pdf

Autophagy-Related Atg8 Localizes to the Apicoplast of the Human Malaria Parasite Plasmodium falciparum 1,2 1 3 4 5 2 Kei Kitamura , Chieko Kishi-Itakura , Takafumi Tsuboi , Shigeharu Sato , Kiyoshi Kita , Nobuo Ohta *, Noboru Mizushima1* 1 Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo, Japan, 2 Department of Environmental Parasitology, Tokyo Medical and Dental University, Tokyo, Japan, 3 Cell-Free Science and Technology Research Center and Venture Business Laboratory, Ehime University, Matsuyama, Ehime, Japan, 4 Division of Parasitology, MRC National Institute for Medical Research, London, United Kingdom, 5 Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Abstract Autophagy is a membrane-mediated degradation process, which is governed by sequential functions of Atg proteins. Although Atg proteins are highly conserved in eukaryotes, protozoa possess only a partial set of Atg proteins. Nonetheless, almost all protozoa have the complete factors belonging to the Atg8 conjugation system, namely, Atg3, Atg4, Atg7, and Atg8. Here, we report the biochemical properties and subcellular localization of the Atg8 protein of the human malaria parasite Plasmodium falciparum (PfAtg8). PfAtg8 is expressed during intra-erythrocytic development and associates with membranes likely as a lipid-conjugated form. Fluorescence microscopy and immunoelectron microscopy show that PfAtg8 localizes to the apicoplast, a four membrane-bound non-photosynthetic plastid. Autophagosome-like structures are not observed in the erythrocytic stages. These data suggest that, although Plasmodium parasites have lost most Atg proteins dur