Mitochondrial aerobic respiration is activated during hair follicle stem cells differentiation and its dysfunction retards hair regeneration

Abstract

Background. Emerging researches 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. And inhibition of mitochondrial synthesis protein resulted in extension of hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how it affects hair regeneration has not been elaborated. Methods. We compared the difference between telogen bulge cells and anagen matrix cells in mitochondrial morphology and activity. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured for evaluating redox balance. Besides, pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were detected 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 poised ROS expression levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration converted from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking held back hair regeneration in vivo. Conclusions. Upon HFSCs differentiation, mitochondria was elongated with more abundant cristae and showed higher activity, accompanied with activated aerobic respiration in differentiated cells for higher energy supply. And dysfunction of mitochondrial respiration delays hair regeneration upon injury.