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Affected energy metabolism under manganese stress governs cellular toxicity

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Affected energy metabolism under manganese stress governs cellular toxicity
 
Creator Kaur, Gursharan
Kumar, Vineet
Arora, Amit
Tomar, Ajay
Ashish, .
Sur, Runa
Dutta, Dipak
 
Subject QR Microbiology
 
Description Excessive manganese exposure is toxic, but a comprehensive biochemical picture of this assault is poorly understood. Whether oxidative stress or reduced energy metabolism under manganese exposure causes toxicity is still a debate. To address this, we chose Δmnt P Escherichia coli, a highly manganese-sensitive strain, in this study. Combining microarray, proteomics, and biochemical analyses, we show that the chronic manganese exposure rewires diverse regulatory and metabolic pathways. Manganese stress affects protein and other macromolecular stability, and envelope biogenesis. Most importantly, manganese exposure disrupts both iron-sulfur cluster and heme-enzyme biogenesis by depleting cellular iron level. Therefore, the compromised function of the iron-dependent enzymes in the tricarboxylic acid cycle, and electron transport chain impede ATP synthesis, leading to severe energy deficiency. Manganese stress also evokes reactive oxygen species, inducing oxidative stress. However, suppressing oxidative stress does not improve oxidative phosphorylation and cell growth. On the contrary, iron supplementation resumed cell growth stimulating oxidative phosphorylation. Therefore, we hypothesize that affected energy metabolism is the primal cause of manganese toxicity.
 
Publisher Nature Publishing Group
 
Date 2017
 
Type Article
PeerReviewed
 
Relation http://dx.doi.org/10.1038/s41598-017-12004-3
http://crdd.osdd.net/open/2060/
 
Identifier Kaur, Gursharan and Kumar, Vineet and Arora, Amit and Tomar, Ajay and Ashish, . and Sur, Runa and Dutta, Dipak (2017) Affected energy metabolism under manganese stress governs cellular toxicity. Scientific Reports, 7. ISSN 2045-2322