ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites

ABSTRACT Plasmodium parasites and related pathogens contain an essential nonphotosynthetic plastid organelle, the apicoplast, derived from secondary endosymbiosis. Intriguingly, a highly conserved eukaryotic protein, autophagy-related protein 8 (ATG8), has an autophagy-independent function in the ap...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Marta Walczak, Suresh M. Ganesan, Jacquin C. Niles, Ellen Yeh
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	ATG8 Plasmodium apicoplast apicoplast biogenesis autophagy malaria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0bbf3f4e334c4ae6bbeeb3bfbd99c9ac
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0bbf3f4e334c4ae6bbeeb3bfbd99c9ac
record_format	dspace
spelling	oai:doaj.org-article:0bbf3f4e334c4ae6bbeeb3bfbd99c9ac2021-11-15T15:53:25ZATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites10.1128/mBio.02021-172150-7511https://doaj.org/article/0bbf3f4e334c4ae6bbeeb3bfbd99c9ac2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02021-17https://doaj.org/toc/2150-7511ABSTRACT Plasmodium parasites and related pathogens contain an essential nonphotosynthetic plastid organelle, the apicoplast, derived from secondary endosymbiosis. Intriguingly, a highly conserved eukaryotic protein, autophagy-related protein 8 (ATG8), has an autophagy-independent function in the apicoplast. Little is known about the novel apicoplast function of ATG8 and its importance in blood-stage Plasmodium falciparum. Using a P. falciparum strain in which ATG8 expression was conditionally regulated, we showed that P. falciparum ATG8 (PfATG8) is essential for parasite replication. Significantly, growth inhibition caused by the loss of PfATG8 was reversed by addition of isopentenyl pyrophosphate (IPP), which was previously shown to rescue apicoplast defects in P. falciparum. Parasites deficient in PfATG8, but whose growth was rescued by IPP, had lost their apicoplast. We designed a suite of functional assays, including a new fluorescence in situ hybridization (FISH) method for detection of the low-copy-number apicoplast genome, to interrogate specific steps in apicoplast biogenesis and detect apicoplast defects which preceded the block in parasite replication. Though protein import and membrane expansion of the apicoplast were unaffected, the apicoplast was not inherited by daughter parasites. Our findings demonstrate that, though multiple autophagy-dependent and independent functions have been proposed for PfATG8, only its role in apicoplast biogenesis is essential in blood-stage parasites. We propose that PfATG8 is required for fission or segregation of the apicoplast during parasite replication. IMPORTANCE Plasmodium parasites, which cause malaria, and related apicomplexan parasites are important human and veterinary pathogens. They are evolutionarily distant from traditional model organisms and possess a unique plastid organelle, the apicoplast, acquired by an unusual eukaryote-eukaryote endosymbiosis which established novel protein/lipid import and organelle inheritance pathways in the parasite cell. Though the apicoplast is essential for parasite survival in all stages of its life cycle, little is known about these novel biogenesis pathways. We show that malaria parasites have adapted a highly conserved protein required for macroautophagy in yeast and mammals to function specifically in apicoplast inheritance. Our finding elucidates a novel mechanism of organelle biogenesis, essential for pathogenesis, in this divergent branch of pathogenic eukaryotes.Marta WalczakSuresh M. GanesanJacquin C. NilesEllen YehAmerican Society for MicrobiologyarticleATG8Plasmodiumapicoplastapicoplast biogenesisautophagymalariaMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	ATG8 Plasmodium apicoplast apicoplast biogenesis autophagy malaria Microbiology QR1-502
spellingShingle	ATG8 Plasmodium apicoplast apicoplast biogenesis autophagy malaria Microbiology QR1-502 Marta Walczak Suresh M. Ganesan Jacquin C. Niles Ellen Yeh ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites
description	ABSTRACT Plasmodium parasites and related pathogens contain an essential nonphotosynthetic plastid organelle, the apicoplast, derived from secondary endosymbiosis. Intriguingly, a highly conserved eukaryotic protein, autophagy-related protein 8 (ATG8), has an autophagy-independent function in the apicoplast. Little is known about the novel apicoplast function of ATG8 and its importance in blood-stage Plasmodium falciparum. Using a P. falciparum strain in which ATG8 expression was conditionally regulated, we showed that P. falciparum ATG8 (PfATG8) is essential for parasite replication. Significantly, growth inhibition caused by the loss of PfATG8 was reversed by addition of isopentenyl pyrophosphate (IPP), which was previously shown to rescue apicoplast defects in P. falciparum. Parasites deficient in PfATG8, but whose growth was rescued by IPP, had lost their apicoplast. We designed a suite of functional assays, including a new fluorescence in situ hybridization (FISH) method for detection of the low-copy-number apicoplast genome, to interrogate specific steps in apicoplast biogenesis and detect apicoplast defects which preceded the block in parasite replication. Though protein import and membrane expansion of the apicoplast were unaffected, the apicoplast was not inherited by daughter parasites. Our findings demonstrate that, though multiple autophagy-dependent and independent functions have been proposed for PfATG8, only its role in apicoplast biogenesis is essential in blood-stage parasites. We propose that PfATG8 is required for fission or segregation of the apicoplast during parasite replication. IMPORTANCE Plasmodium parasites, which cause malaria, and related apicomplexan parasites are important human and veterinary pathogens. They are evolutionarily distant from traditional model organisms and possess a unique plastid organelle, the apicoplast, acquired by an unusual eukaryote-eukaryote endosymbiosis which established novel protein/lipid import and organelle inheritance pathways in the parasite cell. Though the apicoplast is essential for parasite survival in all stages of its life cycle, little is known about these novel biogenesis pathways. We show that malaria parasites have adapted a highly conserved protein required for macroautophagy in yeast and mammals to function specifically in apicoplast inheritance. Our finding elucidates a novel mechanism of organelle biogenesis, essential for pathogenesis, in this divergent branch of pathogenic eukaryotes.
format	article
author	Marta Walczak Suresh M. Ganesan Jacquin C. Niles Ellen Yeh
author_facet	Marta Walczak Suresh M. Ganesan Jacquin C. Niles Ellen Yeh
author_sort	Marta Walczak
title	ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites
title_short	ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites
title_full	ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites
title_fullStr	ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites
title_full_unstemmed	ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites
title_sort	atg8 is essential specifically for an autophagy-independent function in apicoplast biogenesis in blood-stage malaria parasites
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/0bbf3f4e334c4ae6bbeeb3bfbd99c9ac
work_keys_str_mv	AT martawalczak atg8isessentialspecificallyforanautophagyindependentfunctioninapicoplastbiogenesisinbloodstagemalariaparasites AT sureshmganesan atg8isessentialspecificallyforanautophagyindependentfunctioninapicoplastbiogenesisinbloodstagemalariaparasites AT jacquincniles atg8isessentialspecificallyforanautophagyindependentfunctioninapicoplastbiogenesisinbloodstagemalariaparasites AT ellenyeh atg8isessentialspecificallyforanautophagyindependentfunctioninapicoplastbiogenesisinbloodstagemalariaparasites
_version_	1718427256333795328

ATG8 Is Essential Specifically for an Autophagy-Independent Function in Apicoplast Biogenesis in Blood-Stage Malaria Parasites

Ejemplares similares