Using exomarkers to assess mitochondrial reactive species in vivo.

TitleUsing exomarkers to assess mitochondrial reactive species in vivo.
Publication TypeJournal Article
Year of Publication2014
AuthorsLogan, A, Cochemé, HM, Pun, PBoon Li, Apostolova, N, Smith, RAJ, Larsen, L, Larsen, DS, James, AM, Fearnley, IM, Rogatti, S, Prime, TA, Finichiu, PG, Dare, A, Chouchani, ET, Pell, VR, Methner, C, Quin, C, McQuaker, SJ, Krieg, T, Hartley, RC, Murphy, MP
JournalBiochim Biophys Acta
Volume1840
Issue2
Pagination923-30
Date Published2014 Feb
ISSN0006-3002
KeywordsAnimals, Biological Markers, Mice, Mitochondria, Models, Biological, Molecular Probes, Oxidative Stress, Reactive Oxygen Species
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.

DOI10.1016/j.bbagen.2013.05.026
Alternate JournalBiochim. Biophys. Acta
Citation Key10.1016/j.bbagen.2013.05.026
PubMed ID23726990
Grant ListBB/I012923 / / Biotechnology and Biological Sciences Research Council / United Kingdom
BB/I012923/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_U105663142 / / Medical Research Council / United Kingdom