Hsp90 and metal‐binding J‐protein family chaperones are not critically involved in cellular iron–sulfur protein assembly and iron regulation in yeast

• Published in: FEBS letters Vol. 597; no. 13; pp. 1718 - 1732
• Main Authors: Carvalho, Felipe A., Mühlenhoff, Ulrich, Braymer, Joseph J., Root, Vasilij, Stümpfig, Martin, Oliveira, Carla C., Lill, Roland
• Format: Journal Article
• Language: English
• Published: England 01.07.2023
• Subjects: heat shock proteins; HSP90 Heat-Shock Proteins - genetics; HSP90 Heat-Shock Proteins - metabolism; Iron - metabolism; iron chaperones; Iron-Sulfur Proteins - genetics; Iron-Sulfur Proteins - metabolism; iron–sulfur cluster; mitochondria; Mitochondrial Proteins - metabolism; Molecular Chaperones - metabolism; protein folding; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; protein folding; heat shock proteins; iron-sulfur cluster; mitochondria; iron chaperones
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.14612

Systematic studies have revealed interactions between components of the Hsp90 chaperone system and Fe/S protein biogenesis or iron regulation. In addition, two chloroplast‐localized DnaJ‐like proteins, DJA5 and DJA6, function as specific iron donors in plastidial Fe/S protein biogenesis. Here, we used Saccharomyces cerevisiae to study the impact of both the Hsp90 chaperone and the yeast DJA5‐DJA6 homologs, the essential cytosolic Ydj1, and the mitochondrial Mdj1, on cellular iron‐related processes. Despite severe phenotypes induced upon depletion of these crucial proteins, there was no critical in vivo impact on Fe/S protein biogenesis or iron regulation. Importantly, unlike the plant DJA5‐DJA6 iron chaperones, Ydj1 and Mdj1 did not bind iron in vivo, suggesting that these proteins use zinc for function under normal physiological conditions. Genetic and physical interactions between the Hsp90 chaperone and components of iron–sulfur protein biogenesis and iron regulation (shown here by stars) have suggested a critical connection between these biological systems. Moreover, dedicated plastidial J‐proteins have been characterized as iron donors for iron–sulfur protein assembly. Here, the roles of Hsp90 and the J‐proteins Ydj1 and Mdj1 in several iron‐related processes were scrutinized in yeast.