A prototypical small-molecule modulator uncouples mitochondria in response to endogenous hydrogen peroxide production

McQuaker, S. J., Quinlan, C. L., Caldwell, S. T. , Brand, M. D. and Hartley, R. C. (2013) A prototypical small-molecule modulator uncouples mitochondria in response to endogenous hydrogen peroxide production. ChemBioChem, 14(8), pp. 993-1000. (doi:10.1002/cbic.201300115) (PMID:23640856) (PMCID:PMC3743171)

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Abstract

A high membrane potential across the mitochondrial inner membrane leads to the production of the reactive oxygen species (ROS) implicated in aging and age-related diseases. A prototypical drug for the correction of this type of mitochondrial dysfunction is presented. MitoDNP-SUM accumulates in mitochondria in response to the membrane potential due to its mitochondria-targeting alkyltriphenylphosphonium (TPP) cation and is uncaged by endogenous hydrogen peroxide to release the mitochondrial uncoupler, 2,4-dinitrophenol (DNP). DNP is known to reduce the high membrane potential responsible for the production of ROS. The approach potentially represents a general method for the delivery of drugs to the mitochondrial matrix through mitochondria targeting and H2O2-induced uncaging.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Caldwell, Dr Stuart and Hartley, Professor Richard
Authors: McQuaker, S. J., Quinlan, C. L., Caldwell, S. T., Brand, M. D., and Hartley, R. C.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:ChemBioChem
Publisher:Wiley - V C H Verlag GmbH & Co. KGaA
ISSN:1439-4227
ISSN (Online):1439-7633
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in ChemBioChem 14(8):993-1000
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
537551Targeting Ca2+ Signals in intact native smooth muscleRichard HartleyWellcome Trust (WELLCOME)WT0922292MACHEM - CHEMISTRY