Assessing ClO- level during ER stress and cellular senescence through a ratio fluorescent probe with dual organelle targeting ability

More evidence supports that endoplasmic reticulums stress (ER stress) has close relationship with many disease, including Alzheimer’s disease, and such diseases are often closely related to senescence. Both ER stress and senescence involve disorder of redox regulation and may further cause ClO - accumulation. It is of great importance to develop a tool to visualize ralated organelles to investigate the role of ClO - during ER stress or senescence. In this work, a novel dual-targetable ClO - probe RT-ER was designed, and the probe could image endoplasmic reticulums and lysosome by sequence under stimulation of ClO - . RT-ER worked in a ratiometric manner and was extremely sensitive to ClO - ( ~ 484 folds enchancement within 10 s after the stimulation of ClO - ). RT-ER showed great biocompatibility and was further applied in living cells imaging. We demonstrated that RT-ER enables both exogenous and endogenous ClO - imaging. Compared with the commercial dye Lysosome-Tracker Deep Red, RT-ER showed better photobleaching resistance. We successfully used RT-ER to track the interaction between endoplasmic reticulum and lysosome after ClO - accumulation. More importantly, with the help of RT-ER, we further revealed the level of ClO - change during ER stress and senescence, which will facilitate the functional study of ClO - −disease contacts. • The probe could image ERs and lysososme in two channels by sequence with stimulation of ClO - . • The intereactions between lysosome and ER can be long-term tracked by the probe when ClO - continue to accumulate in cells. • The fluctuation of ClO - during ERs stress and senescence can be monitored by the probe.