MitoNeoD: a mitochondria-targeted superoxide probe

Shchepinova, M. M. et al. (2017) MitoNeoD: a mitochondria-targeted superoxide probe. Cell Chemical Biology, 24(10), 1285-1298.e12. (doi:10.1016/j.chembiol.2017.08.003) (PMID:28890317)

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Abstract

Mitochondrial superoxide (O2⋅−) underlies much oxidative damage and redox signaling. Fluorescent probes can detect O2⋅−, but are of limited applicability in vivo, while in cells their usefulness is constrained by side reactions and DNA intercalation. To overcome these limitations, we developed a dual-purpose mitochondrial O2⋅− probe, MitoNeoD, which can assess O2⋅− changes in vivo by mass spectrometry and in vitro by fluorescence. MitoNeoD comprises a O2⋅−-sensitive reduced phenanthridinium moiety modified to prevent DNA intercalation, as well as a carbon-deuterium bond to enhance its selectivity for O2⋅− over non-specific oxidation, and a triphenylphosphonium lipophilic cation moiety leading to the rapid accumulation within mitochondria. We demonstrated that MitoNeoD was a versatile and robust probe to assess changes in mitochondrial O2⋅− from isolated mitochondria to animal models, thus offering a way to examine the many roles of mitochondrial O2⋅− production in health and disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Caldwell, Dr Stuart and Shchepinova, Maria and Senn, Dr Hans and Cairns, Mr Andrew and Hartley, Professor Richard
Authors: Shchepinova, M. M., Cairns, A. G., Prime, T. A., Logan, A., James, A. M., Hall, A. R., Vidoni, S., Arndt, S., Caldwell, S. T., Prag, H. A., Pell, V. A., Krieg, T., Mulvey, J. F., Yadav, P., Cobley, J. N., Bright, T. P., Senn, H. M., Anderson, R. F., Murphy, M. P., and Hartley, R.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Cell Chemical Biology
Publisher:Elsevier Cell Press
ISSN:2451-9456
ISSN (Online):2451-9456
Published Online:07 September 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Cell Chemical Biology 24(10):1285-1298.e12
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
553931Developing chemical mass spectrometry probes to assess the production of reactive oxygen species in vivoRichard HartleyBiotechnology and Biological Sciences Research Council (BBSRC)BB/I012826/1CHEM - CHEMISTRY
710821'Exploring mitochondrial metabolism in health and disease using targeted biological chemistryRichard HartleyWellcome Trust (WELLCOTR)110158/Z/15/ZCHEM - CHEMISTRY
584861EPSRC Doctoral Training Grant 2011-2015Mary Beth KneafseyEngineering and Physical Sciences Research Council (EPSRC)EP/J500434/1VPO VICE PRINCIPAL RESEARCH & ENTERPRISE
419371Quota doctoral training account (DTA)Graeme CookeBiotechnology and Biological Sciences Research Council (BBSRC)BB/D526310/1CHEM - CHEMISTRY

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