Abstract

Mitochondrial pH (pHmito) is intimately related to mitochondrial function, and aberrant values for pHmito are linked to several disease states. We report the design, synthesis, and application of mitokyne 1-the first small molecule pHmito sensor for stimulated Raman scattering (SRS) microscopy. This ratiometric probe can determine subtle changes in pHmito in response to external stimuli and the inhibition of both the electron transport chain and ATP synthase with small molecule inhibitors. In addition, 1 was 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.

Highlights

  • Mitochondrial pH is intimately related to mitochondrial function, and aberrant values for pHmito are linked to several disease states

  • Resting mitochondrial pH is typically alkaline as protons are pumped out of the inner mitochondrial matrix via the electron transport chain (ETC), providing a proton motive force which drives adenosine triphosphate (ATP) synthase.[22−24] ψH+ acts to regulate Ca2+ homeostasis, which, in turn, regulates elements of the tricarboxylic acid (TCA) cycle.[25−27] Alkalinization of pHmito is associated with apoptosis,[28] while acidification is associated with mitochondrial autophagy.[27,29]

  • We report the design, synthesis, and application of mitokyne 1 a small molecule pHmito sensor for stimulated Raman scattering (SRS) microscopy (Figure 1)

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Summary

Introduction

Mitochondrial pH (pHmito) is intimately related to mitochondrial function, and aberrant values for pHmito are linked to several disease states. We report the design, synthesis, and application of mitokyne 1 a small molecule pHmito sensor for SRS microscopy (Figure 1).

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