2020
DOI: 10.1002/glia.23952
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Roles for H+/K+ATPase and zinc transporter 3 in cAMP‐mediated lysosomal acidification in bafilomycin A1‐treated astrocytes

Abstract: Vacuolar ATPase (v‐ATPase) is the main proton pump that acidifies vesicles such as lysosomes. Disruption in the lysosomal localization of v‐ATPase leads to lysosomal dysfunction, thus contributing to the pathogenesis of lysosomal storage disorders and neurodegenerative diseases such as Alzheimer's disease. Recent studies showed that increases in cyclic AMP (cAMP) levels acidify lysosomes and consequently enhance autophagy flux. Although the upregulation of v‐ATPase function may be the key mechanism underlying … Show more

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Cited by 18 publications
(14 citation statements)
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“…Both of these transporters were shown, or proposed, to utilize H + gradient established by ATP6 pumps in order to move zinc. As predicted in this control analysis, SLC30A3 and SLC30A4 show several significant ERC values with the ATP6 components ( Fig 3A, top, red points ), which is consistent with their cellular localization and H + requirements for transport (Lee and Koh, 2021). In contrast, their ERC scores with the mitochondrial components (blue points) were lower, and, in both cases ERC was skewed towards the vacuolar/vesicular/lysosomal H + pump relative to the mitochondrial signal ( Fig 3A, bottom ).…”
Section: Resultssupporting
confidence: 86%
See 1 more Smart Citation
“…Both of these transporters were shown, or proposed, to utilize H + gradient established by ATP6 pumps in order to move zinc. As predicted in this control analysis, SLC30A3 and SLC30A4 show several significant ERC values with the ATP6 components ( Fig 3A, top, red points ), which is consistent with their cellular localization and H + requirements for transport (Lee and Koh, 2021). In contrast, their ERC scores with the mitochondrial components (blue points) were lower, and, in both cases ERC was skewed towards the vacuolar/vesicular/lysosomal H + pump relative to the mitochondrial signal ( Fig 3A, bottom ).…”
Section: Resultssupporting
confidence: 86%
“…Both of these transporters were shown, or proposed, to utilize H + gradient established by ATP6 pumps in order to move zinc. As predicted in this control analysis, SLC30A3 and SLC30A4 show several significant ERC values with the ATP6 components (Fig 3A, top, red points), which is consistent with their cellular localization and H + requirements for transport (Lee and Koh, 2021).…”
Section: Slc30a9 Coevolution With the Mitochondrial Componentssupporting
confidence: 86%
“…The PPARα agonist OEA significantly decreased the number of autophagosomes and increased the number of autolysosomes, and these effects were blocked by BAF. BAF is a specific inhibitor of the vacuolar-type H + -translocating ATPase (V-ATPase) inhibitor and therefore affects the acidification of lysosomes, which then impairs the lysosome function [ 40 ]. Lysosomes are specialized cellular organelles, which are critical for the maturation stage of autophagy.…”
Section: Discussionmentioning
confidence: 99%
“…V‐ATPase is the main proton pump that acidifies vesicles such as lysosomes. PPIs can disrupt the lysosomal localization of V‐ATPase leading to lysosomal dysfunction, thus contributing to the lysosomal storage disorders in order to counter tumours 264 …”
Section: Tumour Microenvironment Is the Main Medium For The Prolifera...mentioning
confidence: 99%
“…PPIs can disrupt the lysosomal localization of V-ATPase leading to lysosomal dysfunction, thus contributing to the lysosomal storage disorders in order to counter tumours. 264 The mammalian target of rapamycin (mTOR) is a highly conservative serine/threonine-protein kinase that belongs to the PI3K-related protein kinase family. 112 MTOR can phosphorylate Atg13 preventing it from interacting with complexes containing Atg1 and Atg17, and inhibiting autophagy assembly so as to reduce radiation resistance.…”
Section: Ppis Display An Anti-tumour Effect Through Autophagymentioning
confidence: 99%