Skip to Main content Skip to Navigation
Journal articles

Disrupting the plastidic iron-sulfur cluster biogenesis pathway in Toxoplasma gondii has pleiotropic effects irreversibly impacting parasite viability

Abstract : Like many other apicomplexan parasites, Toxoplasma gondii contains a plastid harbouring key metabolic pathways, including the sulfur utilization factor (SUF) pathway that is involved in the biosynthesis of iron-sulfur clusters. These cofactors are key for a variety of proteins involved in important metabolic reactions, potentially including plastidic pathways for the synthesis of isoprenoid and fatty acids. It was shown previously that impairing the NFS2 cysteine desulfurase, involved in the first step of the SUF pathway, leads to an irreversible killing of intracellular parasites. However, the metabolic impact of disrupting the pathway remained unexplored. Here, we generated another mutant of this pathway deficient in the SUFC ATPase, and investigated in details the phenotypic consequences of TgNFS2 and TgSUFC depletion on parasite homeostasis. Our analysis confirms that Toxoplasma SUF mutants are severely and irreversibly impacted in division and membrane homeostasis. Our analysis suggests a defect in apicoplast-generated fatty acids. However, we show that increased scavenging from the host or supplementation with exogenous fatty acids do not fully restore parasite growth, suggesting that this is not the primary cause for the demise of the parasites and that other important cellular functions were affected. For instance, we also show that the SUF pathway is key for generating the isoprenoid-derived precursors necessary for the proper targeting of GPI-anchored proteins and for parasite motility. Thus, we conclude plastid-generated iron-sulfur clusters support the functions of proteins involved in several vital downstream cellular pathways, which implies the SUF machinery may be explored for new potential anti-Toxoplasma targets.
Complete list of metadata

https://www.hal.inserm.fr/inserm-03759156
Contributor : Sébastien Besteiro Connect in order to contact the contributor
Submitted on : Tuesday, August 23, 2022 - 6:02:05 PM
Last modification on : Saturday, September 10, 2022 - 3:30:00 AM

File

1-s2.0-S0021925822006858-main....
Publication funded by an institution

Identifiers

Collections

Citation

Eléa Renaud, Sarah Pamukcu, Aude Cerutti, Laurence Berry, Catherine Lemaire-Vieille, et al.. Disrupting the plastidic iron-sulfur cluster biogenesis pathway in Toxoplasma gondii has pleiotropic effects irreversibly impacting parasite viability. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2022, 298 (8), pp.102243. ⟨10.1016/j.jbc.2022.102243⟩. ⟨inserm-03759156⟩

Share

Metrics

Record views

898

Files downloads

7740