| Title: |
Global translational and metabolic remodeling during iron deprivation in Toxoplasma gondii |
| Authors: |
Hanna, Jack C.; Shikha, Shikha; Sloan, Megan A.; Harding, Clare |
| Publisher Information: |
American Society for Microbiology |
| Publication Year: |
2026 |
| Collection: |
University of Glasgow: Enlighten - Publications |
| Description: |
Iron is required to support essential cellular processes. Due to diverse and dynamic host environments, the obligate intracellular parasite Toxoplasma gondii must adapt to iron-limited conditions. To investigate the adaptations critical to parasite survival under these conditions, we conducted proteomic and metabolomic profiling of Toxoplasma cultured in iron-depleted conditions. We find that iron depletion results in remodeling of the parasite proteome and triggers swift translational repression, prior to decreases in the key translational factor ABCE1. In the context of repressed translation, we also observe a significant rewiring of energy metabolism. Iron-depleted Toxoplasma have altered mitochondrial morphology and a profound reduction in mitochondrial respiration. Untargeted metabolomics revealed changes in central carbon metabolism, with the accumulation of intermediates of glycolysis and the tricarboxylic acid (TCA) cycle. Stable isotope labeling revealed that iron deprivation leads to a fundamental disconnect between these pathways, with reduced incorporation of glucose-derived carbon into cellular macromolecules and disruption of the TCA cycle. Instead, iron-deprived parasites continued to take up glucose and maintain glycolysis for energy generation. Limiting glucose availability, either in culture media or by genetic ablation of glucose uptake, caused a significant increase in sensitivity to iron restriction. Conversely, the limitation of mitochondrially metabolized glutamine improved parasite fitness in iron-depleted conditions. Together, our results establish iron as a key regulator of parasite translation and metabolic flexibility and demonstrate an increased reliance on glycolysis for energy generation and survival under acute iron deprivation. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.gla.ac.uk/381643/1/381643.pdf; Hanna, Jack C. , Shikha, Shikha ORCID logoorcid:0000-0002-7878-1463 , Sloan, Megan A. ORCID logoorcid:0000-0001-7659-4069 and Harding, Clare ORCID logoorcid:0000-0002-8428-0374 (2026) Global translational and metabolic remodeling during iron deprivation in Toxoplasma gondii. mBio , (doi:10.1128/mbio.03788-25 ) (PMID:41925342) (Early Online Publication) |
| Availability: |
https://eprints.gla.ac.uk/381643/; https://eprints.gla.ac.uk/381643/1/381643.pdf |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.388C2DDC |
| Database: |
BASE |