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*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Citations (Scopus)
9 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.
Original languageEnglish
Pages (from-to)1285–1298.e12
Number of pages27
JournalCell Chemical Biology
Volume24
Issue number10
Early online date7 Sep 2017
DOIs
Publication statusPublished - 19 Oct 2017

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Mitochondria
Intercalation
Superoxides
Deuterium
DNA
Oxidation-Reduction
Mass spectrometry
Cations
Mass Spectrometry
Animals
Carbon
Animal Models
Fluorescence
Health
Oxidation
phenanthridinium

Cite this

Shchepinova, M. M., Cairns, A. G., Prime, T. A., Logan, A., James, A. M., Hall, A. R., ... Hartley, R. C. (2017). MitoNeoD: a mitochondria-targeted superoxide probe. Cell Chemical Biology, 24(10), 1285–1298.e12. https://doi.org/10.1016/j.chembiol.2017.08.003
Shchepinova, Maria M. ; Cairns, Andrew G. ; Prime, Tracy A. ; Logan, Angela ; James, Andrew M. ; Hall, Andrew R. ; Vidoni, Sara ; Arndt, Sabine ; Caldwell, Stuart T. ; Prag, Hiran A. ; Pell, Victoria R. ; Krieg, Thomas ; Mulvey, John F. ; Yadav, Pooja ; Cobley, James N. ; Bright, Thomas P. ; Senn, Hans M. ; Anderson, Robert F. ; Murphy, Michael P. ; Hartley, Richard C. / MitoNeoD : a mitochondria-targeted superoxide probe. In: Cell Chemical Biology. 2017 ; Vol. 24, No. 10. pp. 1285–1298.e12.
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Shchepinova, MM, Cairns, AG, Prime, TA, Logan, A, James, AM, Hall, AR, Vidoni, S, Arndt, S, Caldwell, ST, Prag, HA, Pell, VR, Krieg, T, Mulvey, JF, Yadav, P, Cobley, JN, Bright, TP, Senn, HM, Anderson, RF, Murphy, MP & Hartley, RC 2017, 'MitoNeoD: a mitochondria-targeted superoxide probe', Cell Chemical Biology, vol. 24, no. 10, pp. 1285–1298.e12. https://doi.org/10.1016/j.chembiol.2017.08.003

MitoNeoD : a mitochondria-targeted superoxide probe. / Shchepinova, Maria M.; Cairns, Andrew G.; Prime, Tracy A.; Logan, Angela; James, Andrew M.; Hall, Andrew R.; Vidoni, Sara; Arndt, Sabine; Caldwell, Stuart T.; Prag, Hiran A.; Pell, Victoria R.; Krieg, Thomas; Mulvey, John F.; Yadav, Pooja; Cobley, James N.; Bright, Thomas P.; Senn, Hans M.; Anderson, Robert F.; Murphy, Michael P.; Hartley, Richard C.

In: Cell Chemical Biology, Vol. 24, No. 10, 19.10.2017, p. 1285–1298.e12.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MitoNeoD

T2 - a mitochondria-targeted superoxide probe

AU - Shchepinova, Maria M.

AU - Cairns, Andrew G.

AU - Prime, Tracy A.

AU - Logan, Angela

AU - James, Andrew M.

AU - Hall, Andrew R.

AU - Vidoni, Sara

AU - Arndt, Sabine

AU - Caldwell, Stuart T.

AU - Prag, Hiran A.

AU - Pell, Victoria R.

AU - Krieg, Thomas

AU - Mulvey, John F.

AU - Yadav, Pooja

AU - Cobley, James N.

AU - Bright, Thomas P.

AU - Senn, Hans M.

AU - Anderson, Robert F.

AU - Murphy, Michael P.

AU - Hartley, Richard C.

PY - 2017/10/19

Y1 - 2017/10/19

N2 - 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.

AB - 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.

U2 - 10.1016/j.chembiol.2017.08.003

DO - 10.1016/j.chembiol.2017.08.003

M3 - Article

VL - 24

SP - 1285–1298.e12

JO - Cell Chemical Biology

JF - Cell Chemical Biology

SN - 2451-9448

IS - 10

ER -

Shchepinova MM, Cairns AG, Prime TA, Logan A, James AM, Hall AR et al. MitoNeoD: a mitochondria-targeted superoxide probe. Cell Chemical Biology. 2017 Oct 19;24(10):1285–1298.e12. https://doi.org/10.1016/j.chembiol.2017.08.003