title: Hydrogen peroxide inactivates the Escherichia coli Isc iron-sulphur assembly system, and OxyR induces the Suf system to compensate.
abstract: Environmental H(2) O(2) creates several injuries in Escherichia coli, including the oxidative conversion of dehydratase [4Fe-4S] clusters to an inactive [3Fe-4S] form. To protect itself, H(2) O(2) -stressed E. coli activates the OxyR regulon. This regulon includes the suf operon, which encodes an alternative to the housekeeping Isc iron-sulphur cluster assembly system. Previously studied [3Fe-4S] clusters are repaired by an Isc/Suf-independent pathway, so the rationale for Suf induction was not obvious. Using strains that cannot scavenge H(2) O(2) , we imposed chronic low-grade stress and found that suf mutants could not maintain the activity of isopropylmalate isomerase, a key iron-sulphur dehydratase. Experiments showed that its damaged cluster was degraded in vivo beyond the [3Fe-4S] state, presumably to an apoprotein form, and thus required a de novo assembly system for reactivation. Surprisingly, submicromolar H(2) O(2) poisoned the Isc machinery, thereby creating a requirement for Suf both to repair the isomerase and to activate nascent Fe-S enzymes in general. The IscS and IscA components of the Isc system are H(2) O(2) -resistant, suggesting that oxidants disrupt Isc by oxidizing clusters as they are assembled on or transferred from the IscU scaffold. Consistent with these results, organisms that are routinely exposed to oxidants rely upon Suf rather than Isc for cluster assembly.
authors.affiliation: Department of Microbiology, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Soojin
authors.initials: S
authors.lastname: Jang
authors.forename: James A
authors.initials: JA
authors.lastname: Imlay
mesh_terms: D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D009876:Operon; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; D012097:Repressor Proteins; C499299:oxyR protein, E coli; D006861:Hydrogen Peroxide