title: Evolution of mitochondrial chaperones utilized in Fe-S cluster biogenesis.
abstract: Biogenesis of Fe-S clusters is an essential process [1]. In both Escherichia coli and Saccharomyces cerevisiae, insertion of clusters into an apoprotein requires interaction between a scaffold protein on which clusters are assembled and a molecular chaperone system--an unusually specialized mitochondrial Hsp70 (mtHsp70) and its J protein cochaperone [2]. It is generally assumed that mitochondria inherited their Fe-S cluster assembly machinery from prokaryotes via the endosymbiosis of a bacterium that led to formation of mitochondria. Indeed, phylogenetic analyses demonstrated that the S. cerevisiae J protein, Jac1, and the scaffold, Isu, are orthologous to their bacterial counterparts [3, 4]. However, our analyses indicate that the specialized mtHsp70, Ssq1, is only present in a subset of fungi; most eukaryotes have a single mtHsp70, Ssc1. We propose that an Hsp70 having a role limited to Fe-S cluster biogenesis arose twice during evolution. In the fungal lineage, the gene encoding multifunctional mtHsp70, Ssc1, was duplicated, giving rise to specialized Ssq1. Therefore, Ssq1 is not orthologous to the specialized Hsp70 from E. coli (HscA), but shares a striking level of convergence at the biochemical level. Thus, in the vast majority of eukaryotes, Jac1 and Isu function with the single, multifunctional mtHsp70 in Fe-S cluster biogenesis.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Brenda
authors.initials: B
authors.lastname: Schilke
authors.forename: Barry
authors.initials: B
authors.lastname: Williams
authors.forename: Helena
authors.initials: H
authors.lastname: Knieszner
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pukszta
authors.forename: Patrick
authors.initials: P
authors.lastname: D'Silva
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Craig
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Marszalek
mesh_terms: D019295:Computational Biology; D004926:Escherichia coli; D019143:Evolution, Molecular; D020440:Gene Duplication; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C121520:ISU1 protein, S cerevisiae; D007506:Iron-Sulfur Proteins; C115914:JAC1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C115913:SSQ1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins