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A role for keratins in supporting mitochondrial organization and function in skin keratinocytes
Mitochondria fulfill essential roles in ATP production, metabolic regulation, calcium signaling, generation of reactive oxygen species (ROS), and additional determinants of cellular health. Recent studies have highlighted a role for mitochondria during cell differentiation, including in skin epiderm...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353162/ https://www.ncbi.nlm.nih.gov/pubmed/32213122 http://dx.doi.org/10.1091/mbc.E19-10-0565 |
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author | Steen, Kaylee Chen, Desu Wang, Fengrong Majumdar, Ritankar Chen, Song Kumar, Surinder Lombard, David B. Weigert, Roberto Zieman, Abigail G. Parent, Carole A. Coulombe, Pierre A. |
author_facet | Steen, Kaylee Chen, Desu Wang, Fengrong Majumdar, Ritankar Chen, Song Kumar, Surinder Lombard, David B. Weigert, Roberto Zieman, Abigail G. Parent, Carole A. Coulombe, Pierre A. |
author_sort | Steen, Kaylee |
collection | PubMed |
description | Mitochondria fulfill essential roles in ATP production, metabolic regulation, calcium signaling, generation of reactive oxygen species (ROS), and additional determinants of cellular health. Recent studies have highlighted a role for mitochondria during cell differentiation, including in skin epidermis. The observation of oxidative stress in keratinocytes from Krt16 null mouse skin, a model for pachyonychia congenita (PC)–associated palmoplantar keratoderma, prompted us to examine the role of Keratin (K) 16 protein and its partner K6 in regulating the structure and function of mitochondria. Electron microscopy revealed major anomalies in mitochondrial ultrastructure in late stage, E18.5, Krt6a/Krt6b null embryonic mouse skin. Follow-up studies utilizing biochemical, metabolic, and live imaging readouts showed that, relative to controls, skin keratinocytes null for Krt6a/Krt6b or Krt16 exhibit elevated ROS, reduced mitochondrial respiration, intracellular distribution differences, and altered movement of mitochondria within the cell. These findings highlight a novel role for K6 and K16 in regulating mitochondrial morphology, dynamics, and function and shed new light on the causes of oxidative stress observed in PC and related keratin-based skin disorders. |
format | Online Article Text |
id | pubmed-7353162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-73531622020-07-30 A role for keratins in supporting mitochondrial organization and function in skin keratinocytes Steen, Kaylee Chen, Desu Wang, Fengrong Majumdar, Ritankar Chen, Song Kumar, Surinder Lombard, David B. Weigert, Roberto Zieman, Abigail G. Parent, Carole A. Coulombe, Pierre A. Mol Biol Cell Brief Reports Mitochondria fulfill essential roles in ATP production, metabolic regulation, calcium signaling, generation of reactive oxygen species (ROS), and additional determinants of cellular health. Recent studies have highlighted a role for mitochondria during cell differentiation, including in skin epidermis. The observation of oxidative stress in keratinocytes from Krt16 null mouse skin, a model for pachyonychia congenita (PC)–associated palmoplantar keratoderma, prompted us to examine the role of Keratin (K) 16 protein and its partner K6 in regulating the structure and function of mitochondria. Electron microscopy revealed major anomalies in mitochondrial ultrastructure in late stage, E18.5, Krt6a/Krt6b null embryonic mouse skin. Follow-up studies utilizing biochemical, metabolic, and live imaging readouts showed that, relative to controls, skin keratinocytes null for Krt6a/Krt6b or Krt16 exhibit elevated ROS, reduced mitochondrial respiration, intracellular distribution differences, and altered movement of mitochondria within the cell. These findings highlight a novel role for K6 and K16 in regulating mitochondrial morphology, dynamics, and function and shed new light on the causes of oxidative stress observed in PC and related keratin-based skin disorders. The American Society for Cell Biology 2020-05-15 /pmc/articles/PMC7353162/ /pubmed/32213122 http://dx.doi.org/10.1091/mbc.E19-10-0565 Text en © 2020 Steen 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 | Brief Reports Steen, Kaylee Chen, Desu Wang, Fengrong Majumdar, Ritankar Chen, Song Kumar, Surinder Lombard, David B. Weigert, Roberto Zieman, Abigail G. Parent, Carole A. Coulombe, Pierre A. A role for keratins in supporting mitochondrial organization and function in skin keratinocytes |
title | A role for keratins in supporting mitochondrial organization and function in skin keratinocytes |
title_full | A role for keratins in supporting mitochondrial organization and function in skin keratinocytes |
title_fullStr | A role for keratins in supporting mitochondrial organization and function in skin keratinocytes |
title_full_unstemmed | A role for keratins in supporting mitochondrial organization and function in skin keratinocytes |
title_short | A role for keratins in supporting mitochondrial organization and function in skin keratinocytes |
title_sort | role for keratins in supporting mitochondrial organization and function in skin keratinocytes |
topic | Brief Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353162/ https://www.ncbi.nlm.nih.gov/pubmed/32213122 http://dx.doi.org/10.1091/mbc.E19-10-0565 |
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