Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism

ABSTRACT Acyl coenzyme A (CoA)-binding protein (ACBP) can bind acyl-CoAs with high specificity and affinity, thus playing multiple roles in cellular functions. Mitochondria of the apicomplexan parasite Toxoplasma gondii have emerged as key organelles for lipid metabolism and signaling transduction....

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Autores principales:	Yong Fu, Xia Cui, Sai Fan, Jing Liu, Xiao Zhang, Yihan Wu, Qun Liu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Toxoplasma gondii acyl-CoA-binding protein cardiolipin metabolism gene disruption protein localization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c0db2dec53f43caa51f1c4513dc39f1
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spelling	oai:doaj.org-article:1c0db2dec53f43caa51f1c4513dc39f12021-11-15T15:58:20ZComprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism10.1128/mBio.01597-182150-7511https://doaj.org/article/1c0db2dec53f43caa51f1c4513dc39f12018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01597-18https://doaj.org/toc/2150-7511ABSTRACT Acyl coenzyme A (CoA)-binding protein (ACBP) can bind acyl-CoAs with high specificity and affinity, thus playing multiple roles in cellular functions. Mitochondria of the apicomplexan parasite Toxoplasma gondii have emerged as key organelles for lipid metabolism and signaling transduction. However, the rationale for how this parasite utilizes acyl-CoA-binding protein to regulate mitochondrial lipid metabolism remains unclear. Here, we show that an ankyrin repeat-containing protein, TgACBP2, is localized to mitochondria and displays active acyl-CoA-binding activities. Dephosphorylation of TgACBP2 is associated with relocation from the plasma membrane to the mitochondria under conditions of regulation of environmental [K+]. Under high [K+] conditions, loss of ACBP2 induced mitochondrial dysfunction and apoptosis-like cell death. Disruption of ACBP2 caused growth and virulence defects in the type II strain but not in type I parasites. Interestingly, mitochondrial association factor-1 (MAF1)-mediated host mitochondrial association (HMA) restored the growth ability of ACBP2-deficient type II parasites. Lipidomics analysis indicated that ACBP2 plays key roles in the cardiolipin metabolism of type II parasites and that MAF1 expression complemented the lipid metabolism defects of ACBP2-deficient type II parasites. In addition, disruption of ACBP2 caused attenuated virulence of Prugniuad (Pru) parasites for mice. Taking the results collectively, these data indicate that ACBP2 is critical for the growth and virulence of type II parasites and for the growth of type I parasites under high [K+] conditions. IMPORTANCE Toxoplasma gondii is one of the most successful human parasites, infecting nearly one-third of the total world population. T. gondii tachyzoites residing within parasitophorous vacuoles (PVs) can acquire fatty acids both via salvage from host cells and via de novo synthesis pathways for membrane biogenesis. However, although fatty acid fluxes are known to exist in this parasite, how fatty acids flow through Toxoplasma lipid metabolic organelles, especially mitochondria, remains unknown. In this study, we demonstrated that Toxoplasma expresses an active ankyrin repeat containing protein TgACBP2 to coordinate cardiolipin metabolism. Specifically, HMA acquisition resulting from heterologous functional expression of MAF1 rescued growth and lipid metabolism defects in ACBP2-deficient type II parasites, manifesting the complementary role of host mitochondria in parasite cardiolipin metabolism. This work highlights the importance of TgACBP2 in parasite cardiolipin metabolism and provides evidence for metabolic association of host mitochondria with T. gondii.Yong FuXia CuiSai FanJing LiuXiao ZhangYihan WuQun LiuAmerican Society for MicrobiologyarticleToxoplasma gondiiacyl-CoA-binding proteincardiolipin metabolismgene disruptionprotein localizationMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toxoplasma gondii acyl-CoA-binding protein cardiolipin metabolism gene disruption protein localization Microbiology QR1-502
spellingShingle	Toxoplasma gondii acyl-CoA-binding protein cardiolipin metabolism gene disruption protein localization Microbiology QR1-502 Yong Fu Xia Cui Sai Fan Jing Liu Xiao Zhang Yihan Wu Qun Liu Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism
description	ABSTRACT Acyl coenzyme A (CoA)-binding protein (ACBP) can bind acyl-CoAs with high specificity and affinity, thus playing multiple roles in cellular functions. Mitochondria of the apicomplexan parasite Toxoplasma gondii have emerged as key organelles for lipid metabolism and signaling transduction. However, the rationale for how this parasite utilizes acyl-CoA-binding protein to regulate mitochondrial lipid metabolism remains unclear. Here, we show that an ankyrin repeat-containing protein, TgACBP2, is localized to mitochondria and displays active acyl-CoA-binding activities. Dephosphorylation of TgACBP2 is associated with relocation from the plasma membrane to the mitochondria under conditions of regulation of environmental [K+]. Under high [K+] conditions, loss of ACBP2 induced mitochondrial dysfunction and apoptosis-like cell death. Disruption of ACBP2 caused growth and virulence defects in the type II strain but not in type I parasites. Interestingly, mitochondrial association factor-1 (MAF1)-mediated host mitochondrial association (HMA) restored the growth ability of ACBP2-deficient type II parasites. Lipidomics analysis indicated that ACBP2 plays key roles in the cardiolipin metabolism of type II parasites and that MAF1 expression complemented the lipid metabolism defects of ACBP2-deficient type II parasites. In addition, disruption of ACBP2 caused attenuated virulence of Prugniuad (Pru) parasites for mice. Taking the results collectively, these data indicate that ACBP2 is critical for the growth and virulence of type II parasites and for the growth of type I parasites under high [K+] conditions. IMPORTANCE Toxoplasma gondii is one of the most successful human parasites, infecting nearly one-third of the total world population. T. gondii tachyzoites residing within parasitophorous vacuoles (PVs) can acquire fatty acids both via salvage from host cells and via de novo synthesis pathways for membrane biogenesis. However, although fatty acid fluxes are known to exist in this parasite, how fatty acids flow through Toxoplasma lipid metabolic organelles, especially mitochondria, remains unknown. In this study, we demonstrated that Toxoplasma expresses an active ankyrin repeat containing protein TgACBP2 to coordinate cardiolipin metabolism. Specifically, HMA acquisition resulting from heterologous functional expression of MAF1 rescued growth and lipid metabolism defects in ACBP2-deficient type II parasites, manifesting the complementary role of host mitochondria in parasite cardiolipin metabolism. This work highlights the importance of TgACBP2 in parasite cardiolipin metabolism and provides evidence for metabolic association of host mitochondria with T. gondii.
format	article
author	Yong Fu Xia Cui Sai Fan Jing Liu Xiao Zhang Yihan Wu Qun Liu
author_facet	Yong Fu Xia Cui Sai Fan Jing Liu Xiao Zhang Yihan Wu Qun Liu
author_sort	Yong Fu
title	Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism
title_short	Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism
title_full	Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism
title_fullStr	Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism
title_full_unstemmed	Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism
title_sort	comprehensive characterization of <italic toggle="yes">toxoplasma</italic> acyl coenzyme a-binding protein tgacbp2 and its critical role in parasite cardiolipin metabolism
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/1c0db2dec53f43caa51f1c4513dc39f1
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Comprehensive Characterization of <italic toggle="yes">Toxoplasma</italic> Acyl Coenzyme A-Binding Protein TgACBP2 and Its Critical Role in Parasite Cardiolipin Metabolism

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