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

doi:10.1016/j.chembiol.2017.08.003

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 journal › Article › peer-review

90 Citations (Scopus)

183 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 language	English
Pages (from-to)	1285–1298.e12
Number of pages	27
Journal	Cell Chemical Biology
Volume	24
Issue number	10
Early online date	7 Sept 2017
DOIs	https://doi.org/10.1016/j.chembiol.2017.08.003
Publication status	Published - 19 Oct 2017

Keywords

Mitochondria
Superoxide
ROS measurement
Mitochondria-targeting
Triphenylphosphonium
MitoSOX
Hydroethidine
Exomarker

Access to Document

10.1016/j.chembiol.2017.08.003Licence: CC BY

Cobley_MitoNeoD_Published_2017Final published version, 4.29 MBLicence: CC BY

Cite this

Shchepinova, M. M., Cairns, A. G., Prime, T. A., Logan, A., James, A. M., Hall, A. R., Vidoni, S., Arndt, S., Caldwell, S. T., Prag, H. A., Pell, V. R., Krieg, T., Mulvey, J. F., Yadav, P., Cobley, J. N., Bright, T. P., Senn, H. M., Anderson, R. F., Murphy, M. P., & 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

@article{12f4e06fb9dd4f18b9a75f95946f7e1b,

title = "MitoNeoD: a mitochondria-targeted superoxide probe",

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.",

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

year = "2017",

month = oct,

day = "19",

doi = "10.1016/j.chembiol.2017.08.003",

language = "English",

volume = "24",

pages = "1285–1298.e12",

journal = "Cell Chemical Biology",

issn = "2451-9456",

publisher = "Elsevier Limited",

number = "10",

}

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

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

SN - 2451-9456

VL - 24

SP - 1285–1298.e12

JO - Cell Chemical Biology

JF - Cell Chemical Biology

IS - 10

ER -

MitoNeoD: a mitochondria-targeted superoxide probe

Abstract

Keywords

Access to Document

Fingerprint

Cite this