title: Lysosomal acidification mechanisms.
abstract: 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.
authors.affiliation: Membrane Transport Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. mindellj@ninds.nih.gov
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Mindell
mesh_terms: D000818:Animals; D001711:Biotransformation / Q000502:physiology; D002412:Cations / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D055724:Electrophysiological Phenomena / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
chemical_list: D002412:Cations; D018118:Chloride Channels; D007477:Ions; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D025262:Vacuolar Proton-Translocating ATPases