Journal article
Toxoplasma gondii Infection Is Associated with Mitochondrial Dysfunction in-Vitro
Frontiers in Cellular and Infection Microbiology, Vol.7
2017
Abstract
Upon invasion of host cells, the ubiquitous pathogen Toxoplasma gondii manipulates several host processes, including re-organization of host organelles, to create a replicative niche. Host mitochondrial association to T. gondii parasitophorous vacuoles is rapid and has roles in modulating host immune responses. Here gene expression profiling of T. gondii infected cells reveals enrichment of genes involved in oxidative phosphorylation (OXPHOS) and mitochondrial dysfunction 6 h post-infection. We identified 11 hub genes (HIF-1α, CASP8, FN1, POU5F1, CD44, ISG15, HNRNPA1, MDM2, RPL35, VHL, and NUPR1) and 10 predicted upstream regulators, including 4 endogenous regulators RICTOR, KDM5A, RB1, and D-glucose. We characterized a number of mitochondrial parameters in T. gondii infected human foreskin fibroblast cells over a 36 h time-course. In addition to the usual rapid recruitment and apparent enlargement of mitochondria around the parasitophorous vacuole we observed fragmented host mitochondria in infected cells, not linked to cellular apoptosis, from 24 h post-infection. An increase in mitochondrial superoxide levels in T. gondii infected cells was observed that required active parasite invasion and peaked at 30 h post-infection. Measurement of OXPHOS proteins showed decreased expression of Complex IV in infected cells at 24 h post-infection, followed by decreased expression of Complexes I and II at 36 h post-infection. No change occurred in Complex V. No difference in host mitochondrial membrane potential between infected and mock-infected cells was observed at any time. Our results show perturbation of host mitochondrial function following T. gondii infection that likely impacts on pathogenesis of disease.
Details
- Title
- Toxoplasma gondii Infection Is Associated with Mitochondrial Dysfunction in-Vitro
- Authors/Creators
- G. Syn (Author/Creator) - The Kids Research Institute AustraliaD. Anderson (Author/Creator) - The Kids Research Institute AustraliaJ.M. Blackwell (Author/Creator) - The Kids Research Institute AustraliaS.E. Jamieson (Author/Creator) - The Kids Research Institute Australia
- Publication Details
- Frontiers in Cellular and Infection Microbiology, Vol.7
- Publisher
- Frontiers Media
- Identifiers
- 991005541397107891
- Copyright
- © 2017 Syn, Anderson, Blackwell and Jamieson.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.217 Parasitology - Malaria, Toxoplasmosis & Coccidiosis
- 1.217.1038 Toxoplasma Gondii
- Web Of Science research areas
- Immunology
- Microbiology
- ESI research areas
- Microbiology