MitoNeoD: A Mitochondria-Targeted Superoxide Probe

Maria M. Shchepinova, Andrew G. Cairns, Tracy A. Prime, Angela Logan, Andrew M. James, Andrew R. Hall, Sara Vidoni, Sabine Arndt, Stuart T. Caldwell, Hiran A. Prag, Victoria R. Pell, Thomas Krieg, John F. Mulvey, Pooja Yadav, James N. Cobley, Thomas P. Bright, Hans M. Senn, Robert F. Anderson, Michael P. Murphy, Richard C. Hartley (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)
29 Downloads (Pure)

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. Current methods to assess mitochondrial O2⋅− cannot be applied in vivo and are artifact prone. Here Shchepinova et al. introduce MitoNeoD, which can be used to assess changes in mitochondrial O2⋅− by fluorescence and by mass spectrometry.

Original languageEnglish
Pages (from-to)1285-1298.e12
Number of pages26
JournalCell Chemical Biology
Volume24
Issue number10
Early online date7 Sep 2017
DOIs
Publication statusPublished - 19 Oct 2017

Keywords

  • exomarker
  • hydroethidine
  • mitochondria
  • mitochondria-targeting
  • MitoSOX
  • ROS measurement
  • superoxide
  • triphenylphosphonium

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