气候变化领域集成服务门户(CCPortal): Toxoplasma gondii association with host mitochondria requires key mitochondrial protein import machinery

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DOI	10.1073/pnas.2013336118
	Toxoplasma gondii association with host mitochondria requires key mitochondrial protein import machinery
	Blank M.L.; Xia J.; Morcos M.M.; Sun M.; Cantrell P.S.; Liu Y.; Zeng X.; Powell C.J.; Yates N.; Boulanger M.J.; Boyle J.P.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Host mitochondrial association (HMA) is a well-known phenomenon during Toxoplasma gondii infection of the host cell. The T. gondii locus mitochondrial association factor 1 (MAF1) is required for HMA and MAF1 encodes distinct paralogs of secreted dense granule effector proteins, some of which mediate the HMA phenotype (MAF1b paralogs drive HMA; MAF1a paralogs do not). To identify host proteins required for MAF1b-mediated HMA, we performed unbiased, label-free quantitative proteomics on host cells infected with type II parasites expressing MAF1b, MAF1a, and an HMA-incompetent MAF1b mutant. Across these samples, we identified ∼1,360 MAF1-interacting proteins, but only 13 that were significantly and uniquely enriched in MAF1b pull-downs. The gene products include multiple mitochondria-associated proteins, including those that traffic to the mitochondrial outer membrane. Based on follow-up endoribonuclease-prepared short interfering RNA (esiRNA) experiments targeting these candidate MAF1btargeted host factors, we determined that the mitochondrial receptor protein TOM70 and mitochondria-specific chaperone HSPA9 were essential mediators of HMA. Additionally, the enrichment of TOM70 at the parasitophorous vacuole membrane interface suggests parasite-driven sequestration of TOM70 by the parasite. These results show that the interface between the T. gondii vacuole and the host mitochondria is characterized by interactions between a single parasite effector and multiple target host proteins, some of which are critical for the HMA phenotype itself. The elucidation of the functional members of this complex will permit us to explain the link between HMA and changes in the biology of the host cell. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Mitochondria \| Toxoplasma gondii \| virulence \| tandem gene expansion \| neofunctionalization
语种	英语
scopus关键词	chaperone; chaperone HSPA9; mitochondrial association factor 1; mitochondrial protein; mitochondrial receptor protein TOM70; protozoal protein; receptor protein; small interfering RNA; unclassified drug; Article; cell organelle; controlled study; host cell; host mitochondrial association; host pathogen interaction; mitochondrion; nonhuman; outer membrane; paralogy; phenotype; priority journal; protein transport; proteomics; quantitative analysis; Toxoplasma gondii; toxoplasmosis; virulence
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180168
作者单位	Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA 15261, United States; Biomedical Mass Spectrometry Center, University of Pittsburgh Schools of the Health Sciences, Pittsburgh, PA 15261, United States; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 5C2, Canada; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States
推荐引用方式 GB/T 7714	Blank M.L.,Xia J.,Morcos M.M.,et al. Toxoplasma gondii association with host mitochondria requires key mitochondrial protein import machinery[J],2021,118(12).
APA	Blank M.L..,Xia J..,Morcos M.M..,Sun M..,Cantrell P.S..,...&Boyle J.P..(2021).Toxoplasma gondii association with host mitochondria requires key mitochondrial protein import machinery.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Blank M.L.,et al."Toxoplasma gondii association with host mitochondria requires key mitochondrial protein import machinery".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).