Cited by 1,258ATP Synthase and ATPases ResearchCellular transport and secretionIon Transport and Channel Regulation

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Lysosomal Acidification Mechanisms

Mindell, Joseph A.·2012·Annual Review of Physiology

DOI 10.1146/annurev-physiol-012110-142317

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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.

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Authors: Mindell, J. A.
Affiliations: National Institutes of Health (US)
Corresponding author: Mindell, Joseph A.
ORCID: Mindell, Joseph A.
Venue: Annual Review of Physiology
Publisher: Annual Reviews
Published: 2012-03-17
Volume: 74
Issue: 1
Pages: 69-86
ISSN: 0066-4278 (ISSN-L)
1545-1585
DOI: 10.1146/annurev-physiol-012110-142317
OpenAlex: W2000678720
Cited by: 1,258
References: 93
Citations by year: 2026: 99 · 2025: 123 · 2024: 133 · 2023: 106 · 2022: 109 · 2021: 113 · 2020: 106 · 2019: 112 · 2018: 83 · 2017: 76 · 2016: 69 · 2015: 51 · 2014: 40 · 2013: 31 · 2012: 5
FWCI: 2.21
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Physiology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords: lysosomal acidification, lysosomal pH, V-type ATPase, proton translocation, counterion transport, ClC-7, cation transport, endocytic pathway, pH control
MeSH terms: Animals, Biotransformation, Cations, Humans, Hydrogen-Ion Concentration, Ions, Lysosomes, Chloride Channels, Cystic Fibrosis Transmembrane Conductance Regulator, Vacuolar Proton-Translocating ATPases, Electrophysiological Phenomena

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