Vacuolar H+-ATPase (V-ATPase) is an ATP-dependent proton pump, which transports protons across the membrane. It is a multi-protein complex which is composed of at least 13 subunits. The Caenorhabditis elegans vha-8 encodes the E subunit of V-ATPase which is expressed in the hypodermis, intestine and H-shaped excretory cells. VHA-8 is necessary for proper intestinal function likely through its role in cellular acidification of intestinal cells. The null mutants of vha-8 show a larval lethal phenotype indicating that vha-8 is an essential gene for larval development in C. elegans. Interestingly, characteristics of necrotic cell death were observed in the hypodermis and intestine of the arrested larvae suggesting that pH homeostasis via the E subunit of V-ATPase is required for the cell survival in C. elegans.
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http://dx.doi.org/10.1016/j.febslet.2006.04.067 | DOI Listing |
iScience
January 2025
Department of Experimental Medicine, University of Genova, Viale Benedetto XV/3, 16132 Genoa, Italy.
The vacuolar ATPase (v-ATPase) is essential for acidification of intracellular organelles, including synaptic vesicles. Its activity is controlled by cycles of association and dissociation of the ATP hydrolysis (V) and proton transport (V) multi-protein subunits. Mutations in genes coding for both v-ATPase subunits and TBC1D24 cause neurodevelopmental disorders with overlapping syndromes; therefore, it is important to investigate their potentially interrelated functions.
View Article and Find Full Text PDFAutophagy
January 2025
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.
J Cell Physiol
January 2025
Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
Megalin is a multiple-ligand receptor that contributes to protein reabsorption in the kidney. Recently, megalin was found to act as a novel endocytic receptor for prorenin. Internalization depended on the (pro)renin receptor.
View Article and Find Full Text PDFNature
December 2024
State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Lithocholic acid (LCA) is accumulated in mammals during calorie restriction and it can activate AMP-activated protein kinase (AMPK) to slow down ageing. However, the molecular details of how LCA activates AMPK and induces these biological effects are unclear. Here we show that LCA enhances the activity of sirtuins to deacetylate and subsequently inhibit vacuolar H-ATPase (v-ATPase), which leads to AMPK activation through the lysosomal glucose-sensing pathway.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Institute of Human Genetics, University Medical Center Göttingen, 37073, Göttingen, Germany.
Loss-of-function variants in ATP6V0A2, encoding the trans Golgi V-ATPase subunit V0a2, cause wrinkly skin syndrome (WSS), a connective tissue disorder with glycosylation defects and aberrant cortical neuron migration. We used knock-out (Atp6v0a2) and knock-in (Atp6v0a2) mice harboring the R755Q missense mutation selectively abolishing V0a2-mediated proton transport to investigate the WSS pathomechanism. Homozygous mutants from both strains displayed a reduction of growth, dermis thickness, and elastic fiber formation compatible with WSS.
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