Compartmentation of Mitochondrial and Oxidative Metabolism in Growing Hair Follicles: A Ring of Fire.
Little is known about the energetics of growing hair follicles, particularly in the mitochondrially abundant bulb. Here, mitochondrial and oxidative metabolism was visualized by multiphoton and light sheet microscopy in cultured bovine hair follicles and plucked human hairs. Mitochondrial membrane potential (ΔΨ), cell viability, reactive oxygen species (ROS), and secretory granules were assessed with parameter-indicating fluorophores. In growing follicles, lower bulb epithelial cells had high viability, and mitochondria were polarized. Most epithelially generated ROS co-localized with polarized mitochondria. As the imaging plane captured more central and distal cells, ΔΨ disappeared abruptly at a transition to a nonfluorescent core continuous with the hair shaft. Approaching the transition, ΔΨ and ROS increased, and secretory granules disappeared. ROS and ΔΨ were strongest in a circumferential paraxial ring at putative sites for formation of the outer cortex/cuticle of the hair shaft. By contrast, polarized mitochondria in dermal papillar fibroblasts produced minimal ROS. Plucked hairs showed a similar abrupt transition of degranulation/depolarization near sites of keratin deposition, as well as an ROS-generating paraxial ring of fire. Hair movement out of the follicle appeared to occur independently of follicular bulb bioenergetics by a tractor mechanism involving the inner and outer root sheaths.
Center for Cell Death, Injury & Regeneration, Departments of Drug Discovery & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA; Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation. Electronic address: JJLemasters@musc.edu.
John J
JJ
Lemasters
Center for Cell Death, Injury & Regeneration, Departments of Drug Discovery & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
Venkat K
VK
Ramshesh
Center for Cell Death, Injury & Regeneration, Departments of Drug Discovery & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA.
Gregory L
GL
Lovelace
Agency for Science, Technology, and Research (A*STAR), Institute for Medical Biology, Singapore.
John
J
Lim
Agency for Science, Technology, and Research (A*STAR), Institute for Medical Biology, Singapore.
Graham D
GD
Wright
AgResearch NZ, Lincoln, Canterbury, New Zealand.
Duane
D
Harland
Center for Cell Death, Injury & Regeneration, Departments of Drug Discovery & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, USA; Agency for Science, Technology, and Research (A*STAR), Institute for Medical Biology, Singapore. Electronic address: Thomas.dawson@imb.a-star.edu.sg.
Thomas L
TL
Dawson
D000818:Animals; D002417:Cattle; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D005347:Fibroblasts; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species