Fe-S Cluster Assembly Pathways in Bacteria

Abstract

SUMMARY Iron-sulfur (Fe-S) clusters are required for critical biochemical pathways, including respiration, photosynthesis, and nitrogen fixation. Assembly of these iron cofactors is a carefully controlled process in cells to avoid toxicity from free iron and sulfide. Multiple Fe-S cluster assembly pathways are present in bacteria to carry out basal cluster assembly, stress-responsive cluster assembly, and enzyme-specific cluster assembly. Although biochemical and genetic characterization is providing a partial picture of in vivo Fe-S cluster assembly, a number of mechanistic questions remain unanswered. Furthermore, new factors involved in Fe-S cluster assembly and repair have recently been identified and are expanding the complexity of current models. Here we attempt to summarize recent advances and to highlight new avenues of research in the field of Fe-S cluster assembly.

Du fer et du soufre dans les protéines

“…Comme nous le verrons, les machineries ISC et SUF ne sont pas de simples duplications l'une de l'autre. Il apparaît donc que, durant l'évolution, plusieurs solutions différentes ont été sélectionnées pour satisfaire les besoins en centres Fe-S des différents organismes [5][6][7][8][9][10]. Enfin, les eucaryotes possèdent une troisième machinerie, la CIA (cytosolic iron-sulfur clusters assembly), que l'on pourrait désigner comme une « extension de la ligne de distribution » de la machinerie ISC, localisée dans le cytoplasme, et requise pour la maturation des protéines cytoplasmiques, voire nucléaires [11,12].…”

“…La machinerie SUF est codée par l'opéron sufABCDSE (Figure 2) [5,6]. L'expression de cet opéron est contrôlée par toute une série de régulateurs transcriptionnels, senseurs de la limitation en fer (Fur), de la présence de formes actives de l'oxygène (OxyR) ou de mono-oxyde d'azote (NsrR).…”

“…Étant donné le rôle central des protéines Fe-S dans le fonctionnement cellulaire, il n'est pas étonnant que des mutations invalidant ou alté-rant le fonctionnement des machineries ISC ou SUF provoquent des phénotypes marqués [5][6][7][8][9][10].…”

The unique regulation of iron-sulfur cluster biogenesis in a Gram-positive bacterium

“…The main role of the Fe/S cluster assembly machineries is to mobilize iron and sulfur atoms from their storage sources, assemble the two components into an Fe/S cluster, and then transfer the newly formed cluster to the final protein acceptors (2). In Escherichia coli, there are two of these Fe/S cluster ''factories,'' the ISC (iron-sulfur cluster) and SUF (sulfur assimilation) systems, whose corresponding genes are organized in two operons, iscSUA-hscBA-fdx and sufABCDSE, respectively (2,3).…”

“…The main role of the Fe/S cluster assembly machineries is to mobilize iron and sulfur atoms from their storage sources, assemble the two components into an Fe/S cluster, and then transfer the newly formed cluster to the final protein acceptors (2). In Escherichia coli, there are two of these Fe/S cluster ''factories,'' the ISC (iron-sulfur cluster) and SUF (sulfur assimilation) systems, whose corresponding genes are organized in two operons, iscSUA-hscBA-fdx and sufABCDSE, respectively (2,3). Deletion mutants of the ISC system display a variety of growth defects due to loss of Fe/S cluster-containing enzyme activity and disruption of sulfur metabolism whereas failure of both the ISC and SUF systems leads to synthetic lethality (4,5).…”