Epithelially Derived, Mitochondrial MPZL3 Negatively Regulates Murine and Human Hair Follicle Cycling

The study presents evidence that Myelin Protein Zero-like 3 (MPZL3), a protein found in the mitochondria, plays a crucial role in the regulation of hair follicle cycling. The research showed that mice lacking MPZL3 experienced accelerated hair follicle cycling, suggesting that MPZL3 normally functions as an inhibitor of anagen entry, the growth phase of the hair cycle. This phenotype was replicated in mice with MPZL3 knockout specifically in the epithelial cells, indicating that the lack of MPZL3 within hair follicle keratinocyte mitochondria drives this effect. In human scalp hair follicle organ culture, MPZL3 knock-down tended to prolong anagen and significantly reduced TGFβ2 expression and dermal papilla fibroblast emigration. MPZL3 silencing also significantly decreased MTCO1 and VDAC/porin protein expression and respiratory chain complex II/IV activity, suggesting that mitochondrial activity and biogenesis may be inhibited. These findings suggest that targeting MPZL3 could be a potential strategy for managing common hair growth disorders.