Organelle-resolved imaging of formaldehyde reveals its spatiotemporal dynamics

Understanding the spatiotemporal dynamics of formaldehyde (FA) is crucial for elucidating its pathophysiology. In this study, we designed a series of organelle-resolved probes to investigate FA dynamics. By incorporating various organelle anchors into a coumarin hydrazonate, we developed a series of probes with excellent organelle selectivity and FA specificity, enabling rapid and precise sensing of FA in an organelle-resolved way. Leveraging these probes, we captured the spatiotemporal dynamics of native FA in response to exogenous FA or oxidative stress challenges. In particular, we unveiled the distinct responses of various organelles to identical cellular stressors. Moreover, we observed the dynamic response within individual organelles when cells were exposed to stressors for varying durations. We envision these probes will serve as versatile tools for probing FA pathophysiology.