Using exomarkers to assess mitochondrial reactive species in vivo
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2013-05-30
Date Acceptance
2013-05-20
Citation
Biochimica et Biophysica Acta - General Subjects, 2013, 1840 (2), pp.923-930
ISSN
0006-3002
Publisher
Elsevier
Start Page
923
End Page
930
Journal / Book Title
Biochimica et Biophysica Acta - General Subjects
Volume
1840
Issue
2
Copyright Statement
© 2013 The Authors. Published by Elsevier B.V. Open access under CC BY license
License URL
Subjects
(3-hydroxybenzyl)triphenylphosphonium bromide
3-(dihydroxyboronyl)benzyltriphenylphosphonium bromide
4-HNE
4-hydroxynonenal
EPR
Exomarker
GFP
Mass spectrometry
MitoB
MitoP
Mitochondria
Oxidative damage
ROS
Reactive oxygen species
SOD
TPMP
TPP
electron paramagnetic resonance
green fluorescent protein
methyltriphenylphosphonium
reactive oxygen species
superoxide dismutase
triphenylphosphonium cation
Animals
Biomarkers
Mice
Models, Biological
Molecular Probes
Oxidative Stress
Reactive Oxygen Species
Biological Markers
Biochemistry & Molecular Biology
06 Biological Sciences
02 Physical Sciences
0601 Biochemistry And Cell Biology
Publication Status
Published