Lysosomal acidification mechanisms

Annu Rev Physiol. 2012;74:69-86. doi: 10.1146/annurev-physiol-012110-142317.


Lysosomes, the terminal organelles on the endocytic pathway, digest macromolecules and make their components available to the cell as nutrients. Hydrolytic enzymes specific to a wide range of targets reside within the lysosome; these enzymes are activated by the highly acidic pH (between 4.5 and 5.0) in the organelles' interior. Lysosomes generate and maintain their pH gradients by using the activity of a proton-pumping V-type ATPase, which uses metabolic energy in the form of ATP to pump protons into the lysosome lumen. Because this activity separates electric charge and generates a transmembrane voltage, another ion must move to dissipate this voltage for net pumping to occur. This so-called counterion may be either a cation (moving out of the lysosome) or an anion (moving into the lysosome). Recent data support the involvement of ClC-7, a Cl(-)/H(+) antiporter, in this process, although many open questions remain as to this transporter's involvement. Although functional results also point to a cation transporter, its molecular identity remains uncertain. Both the V-ATPase and the counterion transporter are likely to be important players in the mechanisms determining the steady-state pH of the lysosome interior. Exciting new results suggest that lysosomal pH may be dynamically regulated in some cell types.

Publication types

  • Review

MeSH terms

  • Animals
  • Biotransformation / physiology
  • Cations / metabolism
  • Chloride Channels / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Electrophysiological Phenomena / physiology
  • Humans
  • Hydrogen-Ion Concentration
  • Ions / metabolism
  • Lysosomes / metabolism
  • Lysosomes / physiology*
  • Vacuolar Proton-Translocating ATPases / chemistry
  • Vacuolar Proton-Translocating ATPases / metabolism
  • Vacuolar Proton-Translocating ATPases / physiology


  • Cations
  • Chloride Channels
  • Ions
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Vacuolar Proton-Translocating ATPases