The P450 system and mTORC1 signalling in acne.

In this issue, Hellmann-Regen et al. suggested that anti-acne effects of erythromycin and tetracyclines may be related to their inhibitory effect of cytochrome P450-mediated degradation of all-trans-retinoic acid (ATRA). We have recently proposed that all anti-acne agents function by attenuation of increased mTORC1 signalling. This commentary links the P450 system to mTORC1 regulation in acne. Drug-mediated induction of P450 activity or P450 mutants with increased catabolic activity may reduce cellular ATRA levels and FoxO1 expression, thus reducing FoxO-mediated mTORC1 inhibition. In contrast, agents blocking ATRA degradation such as erythromycin and tetracyclines may improve acne by increasing FoxO1 expression with consecutive inhibition of mTORC1 signalling.