A Prototypical Small‐Molecule Modulator Uncouples Mitochondria in Response to Endogenous Hydrogen Peroxide Production. Issue 8 (2nd May 2013)

• Record Type: Journal Article
• Authors: McQuaker, Stephen J.; Quinlan, Casey L.; Caldwell, Stuart T.; Brand, Martin D.; Hartley, Richard C.
• Is Part Of: Chembiochem. Volume 14:Issue 8(2013)
• Page Start: 993
• Page End: 1000
• Publication Date: 2013-05-02
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300115
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>