A role for keratins in supporting mitochondrial organization and function in skin keratinocytes
| Autor: | Ritankar Majumdar, Kaylee Steen, Fengrong Wang, David B. Lombard, Desu Chen, Carole A. Parent, Pierre A. Coulombe, Song Chen, Roberto Weigert, Surinder Kumar, A.G. Zieman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Keratinocytes
Male Cellular differentiation Cell Mitochondrion Biology medicine.disease_cause 03 medical and health sciences Mice 0302 clinical medicine Keratoderma Palmoplantar Keratin medicine Pachyonychia congenita Animals Molecular Biology 030304 developmental biology Calcium signaling Skin chemistry.chemical_classification Mice Knockout 0303 health sciences integumentary system Keratin-16 Keratin-6 Cell Biology medicine.disease Cell biology Mitochondria Mice Inbred C57BL Cytoskeletal Proteins Palmoplantar keratoderma medicine.anatomical_structure chemistry Pachyonychia Congenita 030220 oncology & carcinogenesis Mutation Keratins Brief Reports Female Epidermis Oxidative stress |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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