Dual-response fluorescent probe for real-time super-resolution imaging of mitochondrial nucleoprotein dynamics in Parkinson's disease

Abstract

Monitoring the dynamics of mitochondrial nucleoprotein complexes in real-time and at super-resolution is crucial for elucidating their role in Parkinson’s disease, a challenge compounded by the inadequacy of existing fluorescent probes and the complexity of distinguishing mitochondrial proteins and nucleic acids simultaneously. This study introduces a quinolinium derivative probe, selectively enriched in mitochondria and capable of distinct dual fluorescence activation in response to nucleic acids and proteins. This dual-mode function allows for the concurrent visualization of mitochondrial nucleic acids, proteins, and their dynamics. Our super-resolution imaging demonstrates that proteins, primarily localized at mitochondrial cristae, interact with nucleic acids to form and maintain nucleoproteins in a dynamic equilibrium. This equilibrium regulates essential mitochondrial processes such as physiological stress. Notably, we found that Parkinson’s disease progression is marked by the disruption of these nucleoproteins. This research not only paves the way for advanced probe design for detailed mitochondrial imaging but also lays the groundwork for exploring mitochondrial dynamics as therapeutic targets in Parkinson’s disease.