title: Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration.
abstract: Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect hair regeneration has not been elaborated upon. Methods. We compared the difference in mitochondrial morphology and activity between telogen bulge cells and anagen matrix cells. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured to evaluate redox balance. In addition, the level of pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were estimated to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking. Results. During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively stable ROS levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration switched from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking repressed hair regeneration in vivo. Conclusions. Upon HFSCs differentiation, mitochondria are elongated with more abundant cristae and show higher activity, accompanying with activated aerobic respiration in differentiated cells for higher energy supply. Also, dysfunction of mitochondrial respiration delays hair regeneration upon injury.
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Dermatology, The Third Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Binping
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Ben
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Fangfen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Jinmao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Hongfu
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Infectious Diseases and Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University , Changsha, Hunan , China.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
keywords: Differentiation; Hair follicle stem cell; Hair regeneration; Mitochondria; Redox balance