A Novel Link Between Human Hair Follicle Neuroimmunology and Mitochondrial Biology: Substance P Increases Intrafollicular Oxidative Stress and Mitochondrial Biogenesis

Substance P (SP), a neuropeptide associated with emotional stress and neurogenic perifollicular inflammation, has been linked to stress-related hair loss conditions like telogen effluvium and alopecia areata. This study found that SP stimulates the mitochondrial release of reactive oxygen species, impacting human hair follicle (HF) mitochondrial biology. When anagen scalp HFs were treated with SP, there was a significant upregulation of the mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a marker of oxidative phosphorylation, and mitochondrial activity and biogenesis. This was accompanied by increased expression of the mitochondrial mass and biogenesis marker, VDAC1/porin. SP also significantly increased mTORC1 activity, a known promoter of ROS production. These findings suggest a strong mitochondrial response of human scalp HFs to SP, indicating a potential therapeutic intervention with SP antagonists for managing stress-associated human hair greying and hair loss.