Using exomarkers to assess mitochondrial reactive species in vivo

Logan, A. et al. (2014) Using exomarkers to assess mitochondrial reactive species in vivo. Biochimica et Biophysica Acta: General Subjects, 1840(2), pp. 923-930. (doi: 10.1016/j.bbagen.2013.05.026) (PMID:23726990)

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Abstract

Background: The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. Scope of review: One approach towards achieving this goal is the use of exomarkers. In this, exogenous probe compounds are administered to the intact organism and are then transformed by the reactive molecules in vivo to produce a diagnostic exomarker. The exomarker and the precursor probe can be analysed ex vivo to infer the identity and amounts of the reactive species present in vivo. This is akin to the measurement of biomarkers produced by the interaction of reactive species with endogenous biomolecules. Major conclusions and general significance: Our laboratories have developed mitochondria-targeted probes that generate exomarkers that can be analysed ex vivo by mass spectrometry to assess levels of reactive species within mitochondria in vivo. We have used one of these compounds, MitoB, to infer the levels of mitochondrial hydrogen peroxide within flies and mice. Here we describe the development of MitoB and expand on this example to discuss how better probes and exomarkers can be developed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Abbreviations: EPR, electron paramagnetic resonance; GFP, green fluorescent protein; 4-HNE, 4-hydroxynonenal; MitoB, 3-(dihydroxyboronyl)benzyltriphenylphosphonium bromide; MitoP, (3-hydroxybenzyl)triphenylphosphonium bromide; ROS, reactive oxygen species; SOD, superoxide dismutase; TPMP, methyltriphenylphosphonium; TPP, triphenylphosphonium cation

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hartley, Professor Richard and McQuaker, Mr Stephen and Quin, Miss Caroline
Authors: Logan, A., Cochemé, H. M., Li Pun, P. B., Apostolova, N., Smith, R. A.J., Larsen, L., Larsen, D. S., James, A. M., Fearnley, I. M., Rogatti, S., Prime, T. A., Finichiu, P. G., Dare, A., Chouchani, E. T., Pell, V. R., Methner, C., Quin, C., McQuaker, S. J., Krieg, T., Hartley, R. C., and Murphy, M. P.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Biochimica et Biophysica Acta: General Subjects
Publisher:Elsevier B.V.
ISSN:0304-4165
ISSN (Online):1872-8006
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Biochimica et Biophysica Acta: General Subjects 1840(2):923-930
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