The DOI matches its Crossref record; 93 of the 93 references it cites were found in a registry or an index.
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.
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In the citing paper
“Heterozygous progranulin (GRN) mutations are associated with FTD with TDP-43 Type A pathology.79,111”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [111]
In the citing paper
“Lysosomal acidification is maintained principally by the vacuolar-type H ϩ -ATPase complex (vATPase), which imports hydrogen ions into the lysosome (Mindell, 2012).”
From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Mindell, 2012
In the citing paper
“Lysosomal hydrolases are activated by the highly acidic luminal pH (4.5–5.0), which is maintained by the v-ATPase on lysosomal membranes (Mindell, 2012).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Mindell, 2012
Citations
Cites
Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology
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AN INTRODUCTION TO TRP CHANNELS
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Pannexin‐1 mediates large pore formation and interleukin‐1β release by the ATP‐gated P2X7 receptor
Pelegrı́n, P., & Surprenant, A. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601378 · Cited by 1,490
X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity
Dutzler, R., Campbell, E. B., Cadene, M., Chait, B. T., & MacKinnon, R. (2002) · Nature · doi:10.1038/415287a · Cited by 1,446
Loss of the ClC-7 Chloride Channel Leads to Osteopetrosis in Mice and Man
Kornak, U., Kasper, D., Bösl, M. R., Kaiser, E., Schweizer, M., Schulz, A., Friedrich, W., Delling, G., & Jentsch, T. J. (2001) · Cell · doi:10.1016/s0092-8674(01)00206-9 · Cited by 995
Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms
Satyanarayana, A., & Kaldis, P. (2009) · Oncogene · doi:10.1038/onc.2009.170 · Cited by 800
NAADP mobilizes calcium from acidic organelles through two-pore channels
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Gating the Selectivity Filter in ClC Chloride Channels
Dutzler, R., Campbell, E. B., & MacKinnon, R. (2003) · Science · doi:10.1126/science.1082708 · Cited by 727
The ABC protein turned chloride channel whose failure causes cystic fibrosis
Gadsby, D. C., Vergani, P., & Csanády, L. (2006) · Nature · doi:10.1038/nature04712 · Cited by 726
Karet, F. E., Finberg, K. E., Nelson, R. D., Nayır, A., Mocan, H. N., Sanjad, S. A., Rodríguez‐Soriano, J., Santos, F., Cremers, C. W. R. J., Pietro, A. D., et al. (1999) · Nature Genetics · doi:10.1038/5022 · Cited by 687
Cited by
Sorted by citations
Ulbrich, K., Holá, K., Šubr, V., Bakandritsos, A., Tuček, J., & Zbořil, R. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00589 · Cited by 1,759
Signals from the lysosome: a control centre for cellular clearance and energy metabolism
Settembre, C., Fraldi, A., Medina, D. L., & Ballabio, A. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3565 · Cited by 1,755
Molecular definitions of autophagy and related processes
Galluzzi, L., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cecconi, F., Choi, A. M., Chu, C. T., Codogno, P., Colombo, M. I., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201796697 · Cited by 1,646
Lysosomes as dynamic regulators of cell and organismal homeostasis
Ballabio, A., & Bonifacino, J. S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0185-4 · Cited by 1,469
Xu, H., & Ren, D. (2015) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021014-071649 · Cited by 1,067
Metadata
- 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
- 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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