A Unified Intracellular pH Landscape with SITE-pHorin: a Quantum-Entanglement-Enhanced pH Probe

TL;DR

This paper introduces SITE-pHorin, a quantum entanglement-enhanced probe capable of mapping intracellular pH across various organelles with high accuracy, revealing new insights into mitochondrial pH gradients and cellular metabolism.

Contribution

We developed a novel quantum entanglement-based pH probe that provides a unified, wide-range, and quantitative intracellular pH mapping, advancing cellular metabolic studies.

Findings

Measured mitochondrial sub-compartment pH with high precision

Revealed a significant pH gradient between mitochondrial cristae and matrix

Discovered lysosomal pH distribution centered at 4.79

Abstract

An accurate map of intracellular organelle pH is crucial for comprehending cellular metabolism and organellar functions. However, a unified intracellular pH spectrum using a single probe is still lack. Here, we developed a novel quantum entanglement-enhanced pH-sensitive probe called SITE-pHorin, which featured a wide pH-sensitive range and ratiometric quantitative measurement capabilities. Subsequently, we measured the pH of various organelles and their sub-compartments, including mitochondrial sub-spaces, Golgi stacks, endoplasmic reticulum, lysosomes, peroxisomes, and endosomes in COS-7 cells. For the long-standing debate on mitochondrial compartments pH, we measured the pH of mitochondrial cristae as 6.60 \pm 0.40, the pH of mitochondrial intermembrane space as 6.95 \pm 0.30, and two populations of mitochondrial matrix pH at approximately 7.20 \pm 0.27 and 7.50 \pm 0.16, respectively. Notably, the lysosome pH exhibited a single, narrow Gaussian distribution centered at 4.79 \pm 0.17. Furthermore, quantum chemistry computations revealed that both the deprotonation of the residue Y182 and the discrete curvature of deformed benzene ring in chromophore are both necessary for the quantum entanglement mechanism of SITE-pHorin. Intriguingly, our findings reveal an accurate pH gradient (0.6-0.9 pH unit) between mitochondrial cristae and matrix, suggesting prior knowledge about \Delta pH (0.4-0.6) and mitochondrial proton motive force (pmf) are underestimated.