Mitokyne: A Ratiometric Raman Probe for Mitochondrial pH

Abstract

Mitochondrial pH (pHmito) is intimately related to mitochondrial function, and aberrant values for pHmitoare linked to several disease states. We report the design, synthesis, and application of mitokyne1—the first small molecule pHmitosensor for stimulated Raman scattering (SRS) microscopy. This ratiometric probe can determine subtle changes in pHmitoin response to external stimuli and the inhibition of both the electron transport chain and ATP synthase with small molecule inhibitors. In addition,1was also used to monitor mitochondrial dynamics in a time-resolved manner with subcellular spatial resolution during mitophagy providing a powerful tool for dissecting the molecular and cell biology of this critical organelle.