Pyrimidine-Based Fluorescent Probe for Monitoring Mitophagy via Detection of Mitochondrial pH Variation

Impaired mitophagy hinders the clearance of damaged mitochondria, inducing pathological states. Knowledge of this phenomenon is key to diagnosing certain diseases and understanding their pathogenesis. Mitophagy involves an acidization process that could serve as an ideal detection target. In this work, we designed and synthesized a mitochondrial-targeting fluorescence probe, Z2, for evaluating pH variation. This probe exhibited remarkable "turn-on" fluorescence under acidic conditions. In biological applications, Z2 showed a strong, specific pH detection capacity in Parkin-overexpressing HeLa cells during the mitophagy process. The "turn-on" fluorescence property of Z2 was also used to detect pH variations in Caenorhabditis elegans. This probe, as a novel pH assessment tool, may facilitate further research of mitophagy-associated pathological patterns.