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Ubiquinone is a Key Antioxidant during Long Chain Fatty Acid Metabolism in Escherichia coli
Author(s) -
Agrawal Shashank,
Jaswal Kanchan,
Shiver Anthony,
Balecha Himanshi,
Patra Tapas,
Chaba Rachna
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.538.3
Subject(s) - oxidative stress , reactive oxygen species , escherichia coli , antioxidant , biochemistry , oxidative phosphorylation , metabolism , chemistry , bacteria , fatty acid , electron transport chain , biology , gene , genetics
Long chain fatty acids (LCFAs) are a rich source of energy for several bacteria including many important pathogens. However, LCFAs also induce oxidative stress. It is thus important to understand the reason for LCFA mediated oxidative stress and the strategies employed by bacteria to counteract this stress. In this study, we establish that fatty acid uptake and degradation is the reason for LCFA mediated oxidative stress in Escherichia coli . Our genetic screen in E. coli on the LCFA, oleate, and its comparison with published genome‐wide screens on multiple carbon sources reveals that among various electron transport chain (ETC) components, genes involved in the biosynthesis of ubiquinone, an electron carrier in ETC are highly required for growth in LCFAs compared to other carbon sources. Detail genetic and biochemical experiments suggest that the increased requirement of ubiquinone on oleate is to counter elevated levels of reactive oxygen species (ROS) generated by LCFA degradation. Additionally, we find that among various oxidative stress combat players in E. coli , ubiquinone is the major antioxidant and acts as the cell's first line of defense against LCFA‐induced oxidative stress. Intriguingly, we find that whereas the requirement of other ETC components is inversely correlated with the energy yield of non‐fermentable carbon sources, the requirement of ubiquinone correlates with oxidative stress. Our results thus suggest that the known electron carrier function of ubiquinone cannot solely explain the antioxidant role of ubiquinone. The mechanism by which ubiquinone combats ROS would depend on the major site of ROS formation during LCFA degradation. We suggest that FadE, a flavoenzyme involved in β‐oxidation that reduces FAD to FADH 2 could be a predominant site of ROS formation during LCFA metabolism. It is likely that ubiquinone enables the rapid transfer of electrons from FadE to ETC thereby limiting ROS formation. In this direction, we are currently trying to establish the biochemical activity of FadE and its role in re‐oxidizing FADH 2 . Taken together, our studies on the role of ubiquinone during LCFA metabolism would provide a rationale to investigate the contribution of this key ETC component in managing oxidative stress in LCFA‐utilizing pathogenic bacteria. Support or Funding Information This work was supported by start‐up funds from IISER‐Mohali to Rachna Chaba and was partly funded by CSIR Govt. of India to Rachna Chaba. Shashank Agrawal : Supported by a fellowship from IISER‐Mohali for doctoral work. Kanchan Jaswal : Recipient of a DST‐Inspire fellowship for doctoral work. Himanshi Balecha : Supported by a fellowship from DST‐Inspire for undergraduate studies. Tapas Patra : Supported by a fellowship from IISER‐Mohali for postdoctoral work This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .