Targeting mitochondria with small molecules: the preparation of MitoB and MitoP as exomarkers of mitochondrial hydrogen peroxide

Cairns, A. G., McQuaker, S. J., Murphy, M. P. and Hartley, R. C. (2015) Targeting mitochondria with small molecules: the preparation of MitoB and MitoP as exomarkers of mitochondrial hydrogen peroxide. In: Weissig, V. and Edeas, M. (eds.) Mitochondrial Medicine: Volume II, Manipulating Mitochondrial Function. Series: Methods in Molecular Biology, 1265. Springer New York, pp. 25-50. ISBN 9781493922871 (doi:10.1007/978-1-4939-2288-8_3)

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Abstract

Small molecules can be physicochemically targeted to mitochondria using the lipophilic alkyltriphenylphosphonium (TPP) group. Once in the mitochondria the TPP-conjugate can detect or influence processes within the mitochondrial matrix directly. Alternatively, the conjugate can behave as a prodrug, which is activated by release from the TPP group either using an internal or external instruction. Small molecules can be designed that can be used in any cell line, tissue or whole organism, allow temporal control, and be applied in a reversible dose-dependent fashion. An example is the detection and quantification of hydrogen peroxide in mitochondria of whole living organisms by MitoB. Hydrogen peroxide produced within the mitochondrial matrix is involved in signalling and implicated in the oxidative damage associated with aging and a wide range of age-associated conditions including cardiovascular disease, neurodegeneration, and cancer. MitoB accumulates in mitochondria and is converted into the exomarker, MitoP, by hydrogen peroxide in the mitochondrial matrix. The hydrogen peroxide concentration is determined from the ratio of MitoP to MitoB after a period of incubation, and this ratio is determined by mass spectrometry using d15-MitoP and d15-MitoB as standard. Here we describe the synthesis of MitoB and MitoP and the deuterated standards necessary for this method of quantification.

Item Type:Book Sections
Additional Information:Series editor: Walker, J.M.<p></p> The final publication is available at http://link.springer.com/protocol/10.1007%2F978-1-4939-2288-8_3<p></p>
Status:Published
Glasgow Author(s) Enlighten ID:McQuaker, Mr Stephen and Cairns, Mr Andrew and Hartley, Professor Richard
Authors: Cairns, A. G., McQuaker, S. J., Murphy, M. P., and Hartley, R. C.
College/School:College of Science and Engineering > School of Chemistry
Publisher:Springer New York
ISSN:1064-3745
ISBN:9781493922871
Copyright Holders:Copyright © 2015 Springer New York
First Published:First published in Mitochondrial Medicine: Volume II, Manipulating Mitochondrial Function 1265:25-50
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.
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