Toxoplasma gondii Infection Is Associated with Mitochondrial Dysfunction in-Vitro

• DOI: 10.3389/fcimb.2017.00512
• Publication Date: 2017-12-12T07:26:20Z
• Authors: Genevieve Syn; Denise Anderson; Jenefer M. Blackwell; Sarra E. Jamieson
• Keywords: Toxoplasmosis

Upon invasion of host cells, the ubiquitous pathogen Toxoplasma gondii manipulates several processes, including re-organization organelles, to create a replicative niche. Host mitochondrial association T. parasitophorous vacuoles is rapid and has roles in modulating immune responses. Here gene expression profiling infected cells reveals enrichment genes involved oxidative phosphorylation (OXPHOS) dysfunction 6 h post-infection. We identified 11 hub (HIF-1α, CASP8, FN1, POU5F1, CD44, ISG15, HNRNPA1, MDM2, RPL35, VHL, NUPR1) 10 predicted upstream regulators, 4 endogenous regulators RICTOR, KDM5A, RB1, D-glucose. characterized number parameters human foreskin fibroblast over 36 time-course. In addition usual recruitment apparent enlargement mitochondria around vacuole we observed fragmented not linked cellular apoptosis, from 24 An increase superoxide levels was that required active parasite peaked at 30 Measurement OXPHOS proteins showed decreased Complex IV post-infection, followed by Complexes I II No change occurred V. difference membrane potential between mock-infected any time. Our results show perturbation function following infection likely impacts on pathogenesis disease.