Details

Autor(en) / Beteiligte

• 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.

Titel

MitoNeoD: A Mitochondria-Targeted Superoxide Probe

Ist Teil von

• Cell chemical biology, 2017-10, Vol.24 (10), p.1285-1298.e12

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •MitoNeoD is a mitochondria-targeted O2⋅− probe that can be used in vivo•Neopentyl groups prevent DNA intercalation by MitoNeoD and its derivatives•Incorporation of a carbon-deuterium bond enhances O2⋅− selectivity by MitoNeoD•MitoNeoD extends methods available to assess mitochondrial O2⋅− 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.