文献类型：期刊文献

英文题名：Manganese impairs the QoxABCD terminal oxidase leading to respiration-associated toxicity

作者：Sachla, Ankita J.[1];Luo, Yuanchan[1,2];Helmann, John D.[1]

机构：[1]Cornell Univ, Dept Microbiol, 370 Wing Hall,123 Wing Dr, Ithaca, NY 14853 USA;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai, Peoples R China

年份：2021

卷号：116

期号：3

起止页码：729

外文期刊名：MOLECULAR MICROBIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000670023900001)】；

基金：Research reported in this publication was supported by the National Institutes of Health under award number R35GM122461 to JDH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Brian Wendel for ICP-MS instrument operation. We thank Jim Imlay, Lars Hederstedt, and Jim Shapleigh for helpful comments.

语种：英文

外文关键词：cytochrome aa(3); electron transport chain; mhqR; quinol oxidase; respiration

摘要：Cell physiology relies on metalloenzymes and can be easily disrupted by imbalances in metal ion pools. Bacillus subtilis requires manganese for growth and has highly regulated mechanisms for import and efflux that help maintain homeostasis. Cells defective for manganese (Mn) efflux are highly sensitive to intoxication, but the processes impaired by Mn excess are often unknown. Here, we employed a forward genetics approach to identify pathways affected by manganese intoxication. Our results highlight a central role for the membrane-localized electron transport chain in metal intoxication during aerobic growth. In the presence of elevated manganese, there is an increased generation of reactive radical species associated with dysfunction of the major terminal oxidase, the cytochrome aa(3) heme-copper menaquinol oxidase (QoxABCD). Intoxication is suppressed by diversion of menaquinol to alternative oxidases or by a mutation affecting heme A synthesis that is known to convert QoxABCD from an aa(3) to a bo(3)-type oxidase. Manganese sensitivity is also reduced by derepression of the MhqR regulon, which protects cells against reactive quinones. These results suggest that dysfunction of the cytochrome aa(3)-type quinol oxidase contributes to metal-induced intoxication.