@article{1266f59775b44f08b89f596ee1e59718,
title = "A key cytosolic iron–sulfur cluster synthesis protein localizes to the mitochondrion of Toxoplasma gondii",
abstract = "Iron–sulfur (Fe-S) clusters are prosthetic groups on proteins that function in a range of enzymatic and electron transfer reactions. Fe-S cluster synthesis is essential for the survival of all eukaryotes. Independent Fe-S cluster biosynthesis pathways occur in the mitochondrion, plastid, and cytosolic compartments of eukaryotic cells. Little is known about the cytosolic Fe-S cluster biosynthesis in apicomplexan parasites, the causative agents of diseases such as malaria and toxoplasmosis. NBP35 serves as a key scaffold protein on which cytosolic Fe-S clusters assemble, and has a cytosolic localization in most eukaryotes studied thus far. Unexpectedly, we found that the NBP35 homolog of the apicomplexan Toxoplasma gondii (TgNBP35) localizes to the outer mitochondrial membrane, with mitochondrial targeting mediated by an N-terminal transmembrane domain. We demonstrate that TgNBP35 is critical for parasite proliferation, but that, despite its mitochondrial localization, it is not required for Fe-S cluster synthesis in the mitochondrion. Instead, we establish that TgNBP35 is important for the biogenesis of cytosolic Fe-S proteins. Our data are consistent with TgNBP35 playing a central and specific role in cytosolic Fe-S cluster biosynthesis, and imply that the assembly of cytosolic Fe-S clusters occurs on the cytosolic face of the outer mitochondrial membrane in these parasites.",
keywords = "Apicomplexa, iron–sulfur cluster, mitochondria, Toxoplasma",
author = "Aw, {Yi Tong Vincent} and Azadeh Seidi and Hayward, {Jenni A.} and Jiwon Lee and Makota, {F. Victor} and Melanie Rug and {van Dooren}, {Giel G.}",
note = "Funding Information: We thank Harpreet Vohra and Michael Devoy (John Curtin School of Medical Research, ANU) for assistance with fluorescence activated cell sorting, Simona Seizova for generating the ABCE1 3? replacement vector, Lilach Sheiner (U. Glasgow) for sharing unpublished data on TgMys, and the ANU Toxo lab for comments on the manuscript. This research was supported by a Discovery Project from the Australian Research Council to GvD (DP110103144), a Research School of Biology Innovation Fund grant to GvD, an Ideas Grant from the Australian National Health and Medical Research Council to GvD (GNT1182369), and an Australian Government Research Training Program Scholarship to JAH. We also acknowledge the facilities and the assistance of Microscopy Australia at the Centre for Advanced Microscopy (ANU), a facility funded by the ANU, and State and Federal Governments. Funding Information: We thank Harpreet Vohra and Michael Devoy (John Curtin School of Medical Research, ANU) for assistance with fluorescence activated cell sorting, Simona Seizova for generating the ABCE1 3′ replacement vector, Lilach Sheiner (U. Glasgow) for sharing unpublished data on Mys, and the ANU Toxo lab for comments on the manuscript. This research was supported by a Discovery Project from the Australian Research Council to GvD (DP110103144), a Research School of Biology Innovation Fund grant to GvD, an Ideas Grant from the Australian National Health and Medical Research Council to GvD (GNT1182369), and an Australian Government Research Training Program Scholarship to JAH. We also acknowledge the facilities and the assistance of Microscopy Australia at the Centre for Advanced Microscopy (ANU), a facility funded by the ANU, and State and Federal Governments. Tg Publisher Copyright: {\textcopyright} 2020 John Wiley & Sons Ltd",
year = "2021",
month = may,
doi = "10.1111/mmi.14651",
language = "English",
volume = "115",
pages = "968--985",
journal = "Molecular Microbiology",
issn = "0950-382X",
publisher = "Wiley-Blackwell",
number = "5",
}
