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Real-Time Visualizing Mitophagy-Specific Viscosity Dynamic by Mitochondria-Anchored Molecular Rotor

Zou, Zhen, Yan, Qi, Ai, Sixin, Qi, Peng, Yang, Hua, Zhang, Yufei, Qing, Zhihe, Zhang, Lihua, Feng, Feng, Yang, Ronghua
Analytical chemistry 2019 v.91 no.13 pp. 8574-8581
biomarkers, butyrates, fluorescence, image analysis, iodine, metabolism, mitochondria, mitophagy, molecular rotors, pH, rotors, starvation, viscometers, viscosity, water solubility
Mitophagy, as an evolutionarily conserved cellular process, plays a crucial role in preserving cellular metabolism and physiology. Various microenvironment alterations assigned to mitophagy including pH, polarity, and deregulated biomarkers are increasingly understood. However, mitophagy-specific viscosity dynamic in live cells remains a mystery and needs to be explored. Here, a water-soluble mitochondria-targetable molecular rotor, ethyl-4-[3,6-bis(1-methyl-4-vinylpyridium iodine)-9H-carbazol-9-yl)] butanoate (BMVC), was exploited as a fluorescent viscosimeter for imaging viscosity variation during mitophagy. This probe contains two positively charged 1-methyl-4-vinylpyridium components as the rotors, whose rotation will be hindered with the increase of environmental viscosity, resulting in enhancement of fluorescence emission. The results demonstrated that this probe operates well in a mitochondrial microenvironment and displays an off–on fluorescence response to viscosity. By virtue of this probe, new discoveries such as the mitochondrial viscosity will increase during mitophagy are elaborated. The real-time visualization of the mitophagy process under nutrient starvation conditions was also proposed and actualized. We expect this probe would be a robust tool in the pathogenic mechanism research of mitochondrial diseases.