Topical Inhibition of the Electron Transport Chain Can Stimulate the Hair Cycle.

While many signaling pathways have been implicated in control of activation of adult hair follicle stem cells and the hair cycle, less is known about cell intrinsic mechanisms of stem cell control. We previously identified lactate production as a key cell intrinsic regulator of hair follicle stem cell activity, suggesting that cellular metabolism is important in stem cell activation. Others have used transgenic methods to suggest that transgenic blockade of the Electron Transport Chain (ETC) leads to degeneration of the hair follicle. Here, we show that pharmacological abrogation of ETC activity, as opposed to complete ablation of ETC, can promote hair cycle activation without significant cell toxicity. Furthermore, metabolic data suggest that ETC inhibition leads to increased pyruvate accessibility for the Ldh enzyme and therefore increased lactate production, which we previously showed can promote hair cycle activation. Finally, this type of ETC inhibition can even be used to accelerate the hair cycle in aged mice. These results point toward an unexpected and safe method to promote hair follicle stem cell activation.