Activation of the Integrated Stress Response in Human Hair Follicles

This study investigated the effects of inhibiting the Mitochondrial Pyruvate Carrier (MPC) on human hair follicles. Using the inhibitor UK-5099 in short-term ex vivo cultures, researchers observed metabolic stress-induced proliferative arrest in the hair follicle epithelium, including Keratin 15+ epithelial hair follicle stem cells (eHFSCs). Transcriptomic analysis revealed disrupted signalling pathways and mitochondrial dysfunction, leading to the activation of the integrated stress response (ISR) mediated by ATF4. The upregulation of ATF4 and its target gene ADM2 was confirmed, and the ISR inhibitor ISRIB was shown to mitigate these effects. This work highlights the hair follicle's adaptive response to metabolic stress and suggests potential targets for managing hair loss disorders.