Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites

ABSTRACT Mechanisms by which 3′-phosphorylated phosphoinositides (3′-PIPs) regulate the development of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are poorly understood. The catabolic process of autophagy, which is dependent on autophagy-related proteins (ATGs), is one of the...

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Autores principales:	Priyanka Bansal, Anuj Tripathi, Vandana Thakur, Asif Mohmmed, Pushkar Sharma
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Plasmodium falciparum Toxoplasma gondii apicoplast autophagy cell trafficking phosphoinositides Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5026a08d993644a1a33e7421ab6409bc
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spelling	oai:doaj.org-article:5026a08d993644a1a33e7421ab6409bc2021-11-15T15:51:51ZAutophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites10.1128/mBio.01468-172150-7511https://doaj.org/article/5026a08d993644a1a33e7421ab6409bc2017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01468-17https://doaj.org/toc/2150-7511ABSTRACT Mechanisms by which 3′-phosphorylated phosphoinositides (3′-PIPs) regulate the development of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are poorly understood. The catabolic process of autophagy, which is dependent on autophagy-related proteins (ATGs), is one of the major targets of 3′-PIPs in yeast and mammals. In the present study, we identified autophagy-related protein ATG18 as an effector of 3′-PIPs in these parasites. P. falciparum ATG18 (PfATG18) and T. gondii ATG18 (TgATG18) interact with 3′-PIPs but exhibited differences in their specificity of interaction with the ligand PIP. The conditional knockdown of T. gondii or P. falciparum ATG18 (Tg/PfATG18) impaired replication of parasites and resulted in their delayed death. Intriguingly, ATG18 depletion resulted in the loss of the apicomplexan parasite-specific nonphotosynthetic plastid-like organelle apicoplast, which harbors the machinery for biosynthesis of key metabolites, and the interaction of ATG18 to phosphatidylinositol 3-phosphate (PI3P) was critical for apicoplast inheritance. Furthermore, ATG18 regulates membrane association and apicoplast localization of ATG8. These findings provide insights into a novel noncanonical role of ATG18 in apicoplast inheritance. This function of ATG18 in organelle biogenesis is unprecedented in any organism and may be conserved across most apicomplexan parasites. IMPORTANCE Typically, autophagy is a catabolic process utilized by cells for their survival upon encountering nutrient-limiting conditions. The autophagy machinery is very tightly regulated, and autophagy-related genes (ATGs) play a pivotal role in this process. In the present study, we report a novel noncanonical function of autophagy-related protein ATG18 in inheritance of the nonphotosynthetic plastid-like organelle apicoplast in apicomplexan parasites Plasmodium and Toxoplasma. ATG18 depletion in these parasites resulted in “delayed death,” which was the result of loss of apicoplast and impaired parasite division. Pf/TgATG18 interact with 3′-phosphorylated PIPs, which guide their cellular localization in the parasite, which is essential for their function.Priyanka BansalAnuj TripathiVandana ThakurAsif MohmmedPushkar SharmaAmerican Society for MicrobiologyarticlePlasmodium falciparumToxoplasma gondiiapicoplastautophagycell traffickingphosphoinositidesMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Plasmodium falciparum Toxoplasma gondii apicoplast autophagy cell trafficking phosphoinositides Microbiology QR1-502
spellingShingle	Plasmodium falciparum Toxoplasma gondii apicoplast autophagy cell trafficking phosphoinositides Microbiology QR1-502 Priyanka Bansal Anuj Tripathi Vandana Thakur Asif Mohmmed Pushkar Sharma Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites
description	ABSTRACT Mechanisms by which 3′-phosphorylated phosphoinositides (3′-PIPs) regulate the development of apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are poorly understood. The catabolic process of autophagy, which is dependent on autophagy-related proteins (ATGs), is one of the major targets of 3′-PIPs in yeast and mammals. In the present study, we identified autophagy-related protein ATG18 as an effector of 3′-PIPs in these parasites. P. falciparum ATG18 (PfATG18) and T. gondii ATG18 (TgATG18) interact with 3′-PIPs but exhibited differences in their specificity of interaction with the ligand PIP. The conditional knockdown of T. gondii or P. falciparum ATG18 (Tg/PfATG18) impaired replication of parasites and resulted in their delayed death. Intriguingly, ATG18 depletion resulted in the loss of the apicomplexan parasite-specific nonphotosynthetic plastid-like organelle apicoplast, which harbors the machinery for biosynthesis of key metabolites, and the interaction of ATG18 to phosphatidylinositol 3-phosphate (PI3P) was critical for apicoplast inheritance. Furthermore, ATG18 regulates membrane association and apicoplast localization of ATG8. These findings provide insights into a novel noncanonical role of ATG18 in apicoplast inheritance. This function of ATG18 in organelle biogenesis is unprecedented in any organism and may be conserved across most apicomplexan parasites. IMPORTANCE Typically, autophagy is a catabolic process utilized by cells for their survival upon encountering nutrient-limiting conditions. The autophagy machinery is very tightly regulated, and autophagy-related genes (ATGs) play a pivotal role in this process. In the present study, we report a novel noncanonical function of autophagy-related protein ATG18 in inheritance of the nonphotosynthetic plastid-like organelle apicoplast in apicomplexan parasites Plasmodium and Toxoplasma. ATG18 depletion in these parasites resulted in “delayed death,” which was the result of loss of apicoplast and impaired parasite division. Pf/TgATG18 interact with 3′-phosphorylated PIPs, which guide their cellular localization in the parasite, which is essential for their function.
format	article
author	Priyanka Bansal Anuj Tripathi Vandana Thakur Asif Mohmmed Pushkar Sharma
author_facet	Priyanka Bansal Anuj Tripathi Vandana Thakur Asif Mohmmed Pushkar Sharma
author_sort	Priyanka Bansal
title	Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites
title_short	Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites
title_full	Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites
title_fullStr	Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites
title_full_unstemmed	Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites
title_sort	autophagy-related protein atg18 regulates apicoplast biogenesis in apicomplexan parasites
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/5026a08d993644a1a33e7421ab6409bc
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Autophagy-Related Protein ATG18 Regulates Apicoplast Biogenesis in Apicomplexan Parasites

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