Mitochondria immobilized fluorescent probe for dual-emissive monitoring mitophagy based on aggregation/monomer principle

Abstract

Mitophagy plays essential roles in mitochondrial quality control, metabolism regulation, and other crucial biological procedures, and abnormal regulation of mitophagy was directly related to serious diseases. Fluorescent probes are important tools for the visualization and evaluation of mitophagy, but the presented probes were primary based on pH-responsive mechanism, which were significantly interfered by the pH variation in lysosomes and mitochondria. To overcome this, herein, we have for the first time constructed a mitochondria-immobilized probe for dual-emissive visualization of mitophagy based on aggregation/monomer principle. The robust probe was enriched in mitochondria and immobilized via the reaction with thiol group of mitochondrial proteins, and formed aggregates with near-infrared (NIR) fluorescence. During mitophagy, the probe molecules were delivered into autophagolysosomes together with mitochondria, which switched to monomers to give green emission. In this manner, the mitophagy procedure was visualized in dual-emissive mode. With the robust probe, the mitophagy induced by starvation, oxidative stress, and hypoxia has been successfully visualized. In particular, the unique probe enabled monitoring mitophagy on non-pH-responsive mechanism, which can serve as the important complement for the researches on mitophagy.