title: The Fe/S cluster assembly protein Isd11 is essential for tRNA thiolation in Trypanosoma brucei.
abstract: Fe/S clusters are part of the active site of many enzymes and are essential for cell viability. In eukaryotes the cysteine desulfurase Nfs (IscS) donates the sulfur during Fe/S cluster assembly and was thought sufficient for this reaction. Moreover, Nfs is indispensable for tRNA thiolation, a modification generally required for tRNA function and protein synthesis. Recently, Isd11 was discovered as an integral part of the Nfs activity at an early step of Fe/S cluster assembly. Here we show, using a combination of genetic, molecular, and biochemical approaches, that Isd11, in line with its strong association with Nfs, is localized in the mitochondrion of T. brucei. In addition to its involvement in Fe/S assembly, Isd11 also partakes in both cytoplasmic and mitochondrial tRNA thiolation, whereas Mtu1, another protein proposed to collaborate with Nfs in tRNA thiolation, is required for this process solely within the mitochondrion. Taken together these data place Isd11 at the center of these sulfur transactions and raises the possibility of a connection between Fe/S metabolism and protein synthesis, helping integrate two seemingly unrelated pathways.
authors.affiliation: Biology Centre, Institute of Parasitology, Czech Academy of Sciences, and Faculty of Sciences, University of South Bohemia, 37005 Ceské Budejovice (Budweis), Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Paris
authors.forename: Piya
authors.initials: P
authors.lastname: Changmai
authors.forename: Mary Anne T
authors.initials: MA
authors.lastname: Rubio
authors.forename: Alena
authors.initials: A
authors.lastname: Zíková
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Stuart
authors.forename: Juan D
authors.initials: JD
authors.lastname: Alfonzo
authors.forename: Julius
authors.initials: J
authors.lastname: Lukes
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005649:Fumarate Hydratase / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010641:Phenotype; D055550:Protein Stability; D015800:Protozoan Proteins / Q000378:metabolism*; D034622:RNA Interference; D016053:RNA, Protozoan / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*
chemical_list: D007506:Iron-Sulfur Proteins; D024101:Mitochondrial Proteins; D015800:Protozoan Proteins; D016053:RNA, Protozoan; D013438:Sulfhydryl Compounds; D012343:RNA, Transfer; D005649:Fumarate Hydratase; D000154:Aconitate Hydratase