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Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes

The apical surface of the terminally differentiated mammalian urothelial umbrella cell is mechanically stable and highly impermeable, in part due to its coverage by urothelial plaques consisting of 2D crystals of uroplakin particles. The mechanism for regulating the uroplakin/plaque level is unclear...

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Autores principales: Liao, Yi, Tham, Daniel K. L., Liang, Feng-Xia, Chang, Jennifer, Wei, Yuan, Sudhir, Putty-Reddy, Sall, Joseph, Ren, Sarah J., Chicote, Javier U., Arnold, Lora L., Hu, Chih-Chi Andrew, Romih, Rok, Andrade, Leonardo R., Rindler, Michael J., Cohen, Samuel M., DeSalle, Rob, Garcia-España, Antonio, Ding, Mingxiao, Wu, Xue-Ru, Sun, Tung-Tien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857570/
https://www.ncbi.nlm.nih.gov/pubmed/31577526
http://dx.doi.org/10.1091/mbc.E19-05-0284
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author Liao, Yi
Tham, Daniel K. L.
Liang, Feng-Xia
Chang, Jennifer
Wei, Yuan
Sudhir, Putty-Reddy
Sall, Joseph
Ren, Sarah J.
Chicote, Javier U.
Arnold, Lora L.
Hu, Chih-Chi Andrew
Romih, Rok
Andrade, Leonardo R.
Rindler, Michael J.
Cohen, Samuel M.
DeSalle, Rob
Garcia-España, Antonio
Ding, Mingxiao
Wu, Xue-Ru
Sun, Tung-Tien
author_facet Liao, Yi
Tham, Daniel K. L.
Liang, Feng-Xia
Chang, Jennifer
Wei, Yuan
Sudhir, Putty-Reddy
Sall, Joseph
Ren, Sarah J.
Chicote, Javier U.
Arnold, Lora L.
Hu, Chih-Chi Andrew
Romih, Rok
Andrade, Leonardo R.
Rindler, Michael J.
Cohen, Samuel M.
DeSalle, Rob
Garcia-España, Antonio
Ding, Mingxiao
Wu, Xue-Ru
Sun, Tung-Tien
author_sort Liao, Yi
collection PubMed
description The apical surface of the terminally differentiated mammalian urothelial umbrella cell is mechanically stable and highly impermeable, in part due to its coverage by urothelial plaques consisting of 2D crystals of uroplakin particles. The mechanism for regulating the uroplakin/plaque level is unclear. We found that genetic ablation of the highly tissue-specific sorting nexin Snx31, which localizes to plaques lining the multivesicular bodies (MVBs) in urothelial umbrella cells, abolishes MVBs suggesting that Snx31 plays a role in stabilizing the MVB-associated plaques by allowing them to achieve a greater curvature. Strikingly, Snx31 ablation also induces a massive accumulation of uroplakin-containing mitochondria-derived lipid droplets (LDs), which mediate uroplakin degradation via autophagy/lipophagy, leading to the loss of apical and fusiform vesicle plaques. These results suggest that MVBs play an active role in suppressing the excessive/wasteful endocytic degradation of uroplakins. Failure of this suppression mechanism triggers the formation of mitochondrial LDs so that excessive uroplakin membranes can be sequestered and degraded. Because mitochondrial LD formation, which occurs at a low level in normal urothelium, can also be induced by disturbance in uroplakin polymerization due to individual uroplakin knockout and by arsenite, a bladder carcinogen, this pathway may represent an inducible, versatile urothelial detoxification mechanism.
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spelling pubmed-68575702020-01-30 Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes Liao, Yi Tham, Daniel K. L. Liang, Feng-Xia Chang, Jennifer Wei, Yuan Sudhir, Putty-Reddy Sall, Joseph Ren, Sarah J. Chicote, Javier U. Arnold, Lora L. Hu, Chih-Chi Andrew Romih, Rok Andrade, Leonardo R. Rindler, Michael J. Cohen, Samuel M. DeSalle, Rob Garcia-España, Antonio Ding, Mingxiao Wu, Xue-Ru Sun, Tung-Tien Mol Biol Cell Articles The apical surface of the terminally differentiated mammalian urothelial umbrella cell is mechanically stable and highly impermeable, in part due to its coverage by urothelial plaques consisting of 2D crystals of uroplakin particles. The mechanism for regulating the uroplakin/plaque level is unclear. We found that genetic ablation of the highly tissue-specific sorting nexin Snx31, which localizes to plaques lining the multivesicular bodies (MVBs) in urothelial umbrella cells, abolishes MVBs suggesting that Snx31 plays a role in stabilizing the MVB-associated plaques by allowing them to achieve a greater curvature. Strikingly, Snx31 ablation also induces a massive accumulation of uroplakin-containing mitochondria-derived lipid droplets (LDs), which mediate uroplakin degradation via autophagy/lipophagy, leading to the loss of apical and fusiform vesicle plaques. These results suggest that MVBs play an active role in suppressing the excessive/wasteful endocytic degradation of uroplakins. Failure of this suppression mechanism triggers the formation of mitochondrial LDs so that excessive uroplakin membranes can be sequestered and degraded. Because mitochondrial LD formation, which occurs at a low level in normal urothelium, can also be induced by disturbance in uroplakin polymerization due to individual uroplakin knockout and by arsenite, a bladder carcinogen, this pathway may represent an inducible, versatile urothelial detoxification mechanism. The American Society for Cell Biology 2019-11-15 /pmc/articles/PMC6857570/ /pubmed/31577526 http://dx.doi.org/10.1091/mbc.E19-05-0284 Text en © 2019 Liao, Tham, Liang, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Liao, Yi
Tham, Daniel K. L.
Liang, Feng-Xia
Chang, Jennifer
Wei, Yuan
Sudhir, Putty-Reddy
Sall, Joseph
Ren, Sarah J.
Chicote, Javier U.
Arnold, Lora L.
Hu, Chih-Chi Andrew
Romih, Rok
Andrade, Leonardo R.
Rindler, Michael J.
Cohen, Samuel M.
DeSalle, Rob
Garcia-España, Antonio
Ding, Mingxiao
Wu, Xue-Ru
Sun, Tung-Tien
Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
title Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
title_full Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
title_fullStr Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
title_full_unstemmed Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
title_short Mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
title_sort mitochondrial lipid droplet formation as a detoxification mechanism to sequester and degrade excessive urothelial membranes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857570/
https://www.ncbi.nlm.nih.gov/pubmed/31577526
http://dx.doi.org/10.1091/mbc.E19-05-0284
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