A role for keratins in supporting mitochondrial organization and function in skin keratinocytes

• Published in: Molecular biology of the cell Vol. 31; no. 11; pp. 1103 - 1111
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 15.05.2020
• Subjects: Animals; Brief Reports; Cytoskeletal Proteins; Epidermis; Female; Keratin-16 - genetics; Keratin-16 - metabolism; Keratin-6 - genetics; Keratin-6 - metabolism; Keratinocytes - metabolism; Keratinocytes - physiology; Keratins - metabolism; Keratins - physiology; Keratoderma, Palmoplantar; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - metabolism; Mitochondria - physiology; Mutation; Pachyonychia Congenita; Skin - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E19-10-0565

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 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, null embryonic mouse skin. Follow-up studies utilizing biochemical, metabolic, and live imaging readouts showed that, relative to controls, skin keratinocytes null for or 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.