# Organelles harbour pH gradients

## TL;DR

This paper shows that pH is not uniform within certain organelles, challenging previous assumptions and suggesting new ways pH affects cell function.

## Contribution

The discovery of pH gradients within single large organelles and membrane-less structures like the nucleolus is novel.

## Key findings

- pH gradients exist within single large organelles like the ER and mitochondria.
- Membrane-less organelles such as the nucleolus also have pH gradients despite lacking ion-transporting proteins.
- These findings challenge the assumption of uniform pH within individual organelles.

## Abstract

Organelle pH is critical to organelle identity and function. Resident proteins that define each organelle modify transiting cargo proteins, with both retention and trafficking between organelles governed by pH-dependent mechanisms. For example, lysosomal enzymes bind mannose-6-phosphate receptors at the higher pH (~6.5) of the Golgi and dissociate at the lower pH (~5.5) of late endosomes1. Proteins that stray from the endoplasmic reticulum (ER) are captured by KDEL receptors in the acidic Golgi and returned into the neutral ER2,3. This pH-tuned trafficking system compartmentalizes organelle function and prevents mis-localization of critical enzymes4. Dysregulated organelle pH disrupts their function and leads to various diseases. Because protons move rapidly in water, the pH within a single organelle is currently assumed to be spatially uniform5. Here, using a reporter sensitive from pH 5.5 – 10.5 to map a spectrum of organelles at high resolution, we discovered that pH gradients exist within single, large or long organelles such as the ER and mitochondria, and in membrane-less organelles without ion-transporting proteins such as the nucleolus. These new findings upend our understanding of organellar pH, prompting new questions about proton diffusion within the cell, and its potential consequences on organelle function.