<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association

ABSTRACT Many diverse intracellular pathogens, such as Legionella pneumophila, Chlamydia psittaci, Encephalitozoon sp., and Toxoplasma gondii, manipulate and relocate host cell organelles, including mitochondria. Toxoplasma tachyzoites use a secreted protein, mitochondrial association factor 1b (MAF...

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Autores principales:	Felice D. Kelly, Brian M. Wei, Alicja M. Cygan, Michelle L. Parker, Martin J. Boulanger, John C. Boothroyd
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Toxoplasma gondii host-pathogen interactions mitochondria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e04856649aa34bbc865a6614bc11f382
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spelling	oai:doaj.org-article:e04856649aa34bbc865a6614bc11f3822021-11-15T15:21:47Z<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association10.1128/mSphere.00183-172379-5042https://doaj.org/article/e04856649aa34bbc865a6614bc11f3822017-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00183-17https://doaj.org/toc/2379-5042ABSTRACT Many diverse intracellular pathogens, such as Legionella pneumophila, Chlamydia psittaci, Encephalitozoon sp., and Toxoplasma gondii, manipulate and relocate host cell organelles, including mitochondria. Toxoplasma tachyzoites use a secreted protein, mitochondrial association factor 1b (MAF1b), to drive the association between the host mitochondria and the membrane of the parasitophorous vacuole, in which the parasites grow. The identity of the host partner in this interaction, however, has not previously been identified. By exogenously expressing tagged MAF1b in mouse embryonic fibroblasts, we were able to isolate host cell proteins that specifically interact with MAF1b. We then verified these interactions in the MAF1b-expressing fibroblasts, as well as in the context of parasite infection in human fibroblasts and HeLa cells. The results show that a host cell mitochondrial complex, the mitochondrial intermembrane space bridging (MIB) complex, specifically interacts with MAF1b. We further demonstrate that a version of MAF1b that is deficient in host-mitochondrial association does not efficiently coprecipitate the MIB complex. Validation of the importance of the MAF1b-MIB interaction came from showing that knockdown of two MIB complex components, MIC60 and SAM50, substantially reduces mitochondrial association with the parasitophorous vacuole membrane. This interaction between a secreted membrane-integral parasite protein and a membrane-bound complex of a host organelle represents the first instance of organelle relocalization in which both the host and pathogen molecules are known and provides the foundation for more detailed biochemical studies. IMPORTANCE Parasites interact intimately with their hosts, and the interactions shape both parties. The common human parasite Toxoplasma gondii replicates exclusively in a vacuole in a host cell and alters its host cell’s environment through secreted proteins. One of these secreted proteins, MAF1b, acts to concentrate mitochondria around the parasite’s vacuole, and this relocalization alters the host immune response. Many other intracellular pathogens also recruit host mitochondria, but the identities of the partners that mediate this interaction have not previously been described in any infection. Here, we show that Toxoplasma MAF1b binds to the multifunctional MIB protein complex on the host mitochondria. Reducing the levels of the proteins in this mitochondrial complex reduces the close association of host cell mitochondria and the parasite’s vacuole. This work provides new insight into a key host-pathogen interaction and identifies possible targets for future therapeutic intervention as well as a more molecular understanding of important biology.Felice D. KellyBrian M. WeiAlicja M. CyganMichelle L. ParkerMartin J. BoulangerJohn C. BoothroydAmerican Society for MicrobiologyarticleToxoplasma gondiihost-pathogen interactionsmitochondriaMicrobiologyQR1-502ENmSphere, Vol 2, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toxoplasma gondii host-pathogen interactions mitochondria Microbiology QR1-502
spellingShingle	Toxoplasma gondii host-pathogen interactions mitochondria Microbiology QR1-502 Felice D. Kelly Brian M. Wei Alicja M. Cygan Michelle L. Parker Martin J. Boulanger John C. Boothroyd <named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association
description	ABSTRACT Many diverse intracellular pathogens, such as Legionella pneumophila, Chlamydia psittaci, Encephalitozoon sp., and Toxoplasma gondii, manipulate and relocate host cell organelles, including mitochondria. Toxoplasma tachyzoites use a secreted protein, mitochondrial association factor 1b (MAF1b), to drive the association between the host mitochondria and the membrane of the parasitophorous vacuole, in which the parasites grow. The identity of the host partner in this interaction, however, has not previously been identified. By exogenously expressing tagged MAF1b in mouse embryonic fibroblasts, we were able to isolate host cell proteins that specifically interact with MAF1b. We then verified these interactions in the MAF1b-expressing fibroblasts, as well as in the context of parasite infection in human fibroblasts and HeLa cells. The results show that a host cell mitochondrial complex, the mitochondrial intermembrane space bridging (MIB) complex, specifically interacts with MAF1b. We further demonstrate that a version of MAF1b that is deficient in host-mitochondrial association does not efficiently coprecipitate the MIB complex. Validation of the importance of the MAF1b-MIB interaction came from showing that knockdown of two MIB complex components, MIC60 and SAM50, substantially reduces mitochondrial association with the parasitophorous vacuole membrane. This interaction between a secreted membrane-integral parasite protein and a membrane-bound complex of a host organelle represents the first instance of organelle relocalization in which both the host and pathogen molecules are known and provides the foundation for more detailed biochemical studies. IMPORTANCE Parasites interact intimately with their hosts, and the interactions shape both parties. The common human parasite Toxoplasma gondii replicates exclusively in a vacuole in a host cell and alters its host cell’s environment through secreted proteins. One of these secreted proteins, MAF1b, acts to concentrate mitochondria around the parasite’s vacuole, and this relocalization alters the host immune response. Many other intracellular pathogens also recruit host mitochondria, but the identities of the partners that mediate this interaction have not previously been described in any infection. Here, we show that Toxoplasma MAF1b binds to the multifunctional MIB protein complex on the host mitochondria. Reducing the levels of the proteins in this mitochondrial complex reduces the close association of host cell mitochondria and the parasite’s vacuole. This work provides new insight into a key host-pathogen interaction and identifies possible targets for future therapeutic intervention as well as a more molecular understanding of important biology.
format	article
author	Felice D. Kelly Brian M. Wei Alicja M. Cygan Michelle L. Parker Martin J. Boulanger John C. Boothroyd
author_facet	Felice D. Kelly Brian M. Wei Alicja M. Cygan Michelle L. Parker Martin J. Boulanger John C. Boothroyd
author_sort	Felice D. Kelly
title	<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association
title_short	<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association
title_full	<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association
title_fullStr	<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association
title_full_unstemmed	<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association
title_sort	<named-content content-type="genus-species">toxoplasma gondii</named-content> maf1b binds the host cell mib complex to mediate mitochondrial association
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/e04856649aa34bbc865a6614bc11f382
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<named-content content-type="genus-species">Toxoplasma gondii</named-content> MAF1b Binds the Host Cell MIB Complex To Mediate Mitochondrial Association

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