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MitoNeoD: A Mitochondria-Targeted Superoxide Probe.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Shchepinova, Maria M 
Cairns, Andrew G 
Prime, Tracy A 
Logan, Angela 
James, Andrew M 

Abstract

Mitochondrial superoxide (O2⋅-) underlies much oxidative damage and redox signaling. Fluorescent probes can detect O2⋅-, but are of limited applicability in vivo, while in cells their usefulness is constrained by side reactions and DNA intercalation. To overcome these limitations, we developed a dual-purpose mitochondrial O2⋅- probe, MitoNeoD, which can assess O2⋅- changes in vivo by mass spectrometry and in vitro by fluorescence. MitoNeoD comprises a O2⋅--sensitive reduced phenanthridinium moiety modified to prevent DNA intercalation, as well as a carbon-deuterium bond to enhance its selectivity for O2⋅- over non-specific oxidation, and a triphenylphosphonium lipophilic cation moiety leading to the rapid accumulation within mitochondria. We demonstrated that MitoNeoD was a versatile and robust probe to assess changes in mitochondrial O2⋅- from isolated mitochondria to animal models, thus offering a way to examine the many roles of mitochondrial O2⋅- production in health and disease.

Description

Keywords

MitoSOX, ROS measurement, exomarker, hydroethidine, mitochondria, mitochondria-targeting, superoxide, triphenylphosphonium, Animals, Biological Transport, Cell Line, DNA, Male, Mass Spectrometry, Mice, Mitochondria, Models, Molecular, Molecular Probes, Nucleic Acid Conformation, Oxidation-Reduction, Superoxides

Journal Title

Cell Chem Biol

Conference Name

Journal ISSN

2451-9456
2451-9448

Volume Title

24

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_U105663142)
Wellcome Trust (110159/Z/15/Z)