Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>

ABSTRACT Autophagy is a catabolic process widely conserved among eukaryotes that permits the rapid degradation of unwanted proteins and organelles through the lysosomal pathway. This mechanism involves the formation of a double-membrane structure called the autophagosome that sequesters cellular com...

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Autores principales:	Maude F. Lévêque, Laurence Berry, Michael J. Cipriano, Hoa-Mai Nguyen, Boris Striepen, Sébastien Besteiro
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Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/677d0c1f546e4c2da1ccfd48aca86707
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spelling	oai:doaj.org-article:677d0c1f546e4c2da1ccfd48aca867072021-11-15T15:41:23ZAutophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>10.1128/mBio.01446-152150-7511https://doaj.org/article/677d0c1f546e4c2da1ccfd48aca867072015-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01446-15https://doaj.org/toc/2150-7511ABSTRACT Autophagy is a catabolic process widely conserved among eukaryotes that permits the rapid degradation of unwanted proteins and organelles through the lysosomal pathway. This mechanism involves the formation of a double-membrane structure called the autophagosome that sequesters cellular components to be degraded. To orchestrate this process, yeasts and animals rely on a conserved set of autophagy-related proteins (ATGs). Key among these factors is ATG8, a cytoplasmic protein that is recruited to nascent autophagosomal membranes upon the induction of autophagy. Toxoplasma gondii is a potentially harmful human pathogen in which only a subset of ATGs appears to be present. Although this eukaryotic parasite seems able to generate autophagosomes upon stresses such as nutrient starvation, the full functionality and biological relevance of a canonical autophagy pathway are as yet unclear. Intriguingly, in T. gondii, ATG8 localizes to the apicoplast under normal intracellular growth conditions. The apicoplast is a nonphotosynthetic plastid enclosed by four membranes resulting from a secondary endosymbiosis. Using superresolution microscopy and biochemical techniques, we show that TgATG8 localizes to the outermost membrane of this organelle. We investigated the unusual function of TgATG8 at the apicoplast by generating a conditional knockdown mutant. Depletion of TgATG8 led to rapid loss of the organelle and subsequent intracellular replication defects, indicating that the protein is essential for maintaining apicoplast homeostasis and thus for survival of the tachyzoite stage. More precisely, loss of TgATG8 led to abnormal segregation of the apicoplast into the progeny because of a loss of physical interactions of the organelle with the centrosomes. IMPORTANCE By definition, autophagy is a catabolic process that leads to the digestion and recycling of eukaryotic cellular components. The molecular machinery of autophagy was identified mainly in model organisms such as yeasts but remains poorly characterized in phylogenetically distant apicomplexan parasites. We have uncovered an unusual function for autophagy-related protein ATG8 in Toxoplasma gondii: TgATG8 is crucial for normal replication of the parasite inside its host cell. Seemingly unrelated to the catabolic autophagy process, TgATG8 associates with the outer membrane of the nonphotosynthetic plastid harbored by the parasite called the apicoplast, and there it plays an important role in the centrosome-driven inheritance of the organelle during cell division. This not only reveals an unexpected function for an autophagy-related protein but also sheds new light on the division process of an organelle that is vital to a group of important human and animal pathogens.Maude F. LévêqueLaurence BerryMichael J. CiprianoHoa-Mai NguyenBoris StriepenSébastien BesteiroAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 6 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Maude F. Lévêque Laurence Berry Michael J. Cipriano Hoa-Mai Nguyen Boris Striepen Sébastien Besteiro Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>
description	ABSTRACT Autophagy is a catabolic process widely conserved among eukaryotes that permits the rapid degradation of unwanted proteins and organelles through the lysosomal pathway. This mechanism involves the formation of a double-membrane structure called the autophagosome that sequesters cellular components to be degraded. To orchestrate this process, yeasts and animals rely on a conserved set of autophagy-related proteins (ATGs). Key among these factors is ATG8, a cytoplasmic protein that is recruited to nascent autophagosomal membranes upon the induction of autophagy. Toxoplasma gondii is a potentially harmful human pathogen in which only a subset of ATGs appears to be present. Although this eukaryotic parasite seems able to generate autophagosomes upon stresses such as nutrient starvation, the full functionality and biological relevance of a canonical autophagy pathway are as yet unclear. Intriguingly, in T. gondii, ATG8 localizes to the apicoplast under normal intracellular growth conditions. The apicoplast is a nonphotosynthetic plastid enclosed by four membranes resulting from a secondary endosymbiosis. Using superresolution microscopy and biochemical techniques, we show that TgATG8 localizes to the outermost membrane of this organelle. We investigated the unusual function of TgATG8 at the apicoplast by generating a conditional knockdown mutant. Depletion of TgATG8 led to rapid loss of the organelle and subsequent intracellular replication defects, indicating that the protein is essential for maintaining apicoplast homeostasis and thus for survival of the tachyzoite stage. More precisely, loss of TgATG8 led to abnormal segregation of the apicoplast into the progeny because of a loss of physical interactions of the organelle with the centrosomes. IMPORTANCE By definition, autophagy is a catabolic process that leads to the digestion and recycling of eukaryotic cellular components. The molecular machinery of autophagy was identified mainly in model organisms such as yeasts but remains poorly characterized in phylogenetically distant apicomplexan parasites. We have uncovered an unusual function for autophagy-related protein ATG8 in Toxoplasma gondii: TgATG8 is crucial for normal replication of the parasite inside its host cell. Seemingly unrelated to the catabolic autophagy process, TgATG8 associates with the outer membrane of the nonphotosynthetic plastid harbored by the parasite called the apicoplast, and there it plays an important role in the centrosome-driven inheritance of the organelle during cell division. This not only reveals an unexpected function for an autophagy-related protein but also sheds new light on the division process of an organelle that is vital to a group of important human and animal pathogens.
format	article
author	Maude F. Lévêque Laurence Berry Michael J. Cipriano Hoa-Mai Nguyen Boris Striepen Sébastien Besteiro
author_facet	Maude F. Lévêque Laurence Berry Michael J. Cipriano Hoa-Mai Nguyen Boris Striepen Sébastien Besteiro
author_sort	Maude F. Lévêque
title	Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_short	Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_full	Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_fullStr	Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_full_unstemmed	Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>
title_sort	autophagy-related protein atg8 has a noncanonical function for apicoplast inheritance in <named-content content-type="genus-species">toxoplasma gondii</named-content>
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/677d0c1f546e4c2da1ccfd48aca86707
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Autophagy-Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in <named-content content-type="genus-species">Toxoplasma gondii</named-content>

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