Mitochondrial superoxide (O2⋅−) underlies much oxidative damage and redox signaling. Fluorescent probes can detect O2⋅−, but are of limited applicabilityin 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⋅−changesin vivoby mass spectrometry andin vitroby 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.

中文翻译：

---

MitoNeoD：一种以线粒体为目标的超氧化物探针

线粒体超氧化物 (O2⋅−) 是许多氧化损伤和氧化还原信号传导的基础。荧光探针可以检测 O2⋅-，但在体内的适用性有限，而在细胞中，它们的有用性受到副反应和 DNA 嵌入的限制。为了克服这些限制，我们开发了一种两用线粒体 O2⋅-探针 MitoNeoD，它可以通过质谱法和体外荧光法评估体内 O2⋅-变化。MitoNeoD 包含一个对 O2⋅- 敏感的还原菲啶部分，经过修饰以防止 DNA 嵌入，以及一个碳-氘键以增强其对 O2⋅- 的选择性，而不是非特异性氧化，以及一个三苯基鏻亲脂性阳离子部分，导致快速积累线粒体内。