EPAS1/HIF-2α is a driver of mammalian pexophagy

Oxygen (O-2) is an essential substrate in cellular metabolism and signaling and as such is linked to the survival and normal function of metazoans. Central to the molecular mechanisms underlying O-2 homeostasis are hypoxia-inducible factors (HIFs), heterodimeric transcription factors composed of O-2-regulated subunits (HIF1A/HIF-1 or EPAS1/HIF-2), and a constitutively expressed ARNT/HIF-1 subunit, that serve as master regulators of the adaptive response to hypoxia. HIF1A and EPAS1 have both unique and overlapping functions in the regulation of diverse cellular processes, but so far there has been no evidence linking HIF signaling to peroxisomes. In a recent study we identified a unique function of EPAS1 as promoter of pexophagy in hepatocytes. Here we summarize our findings and discuss potential mechanisms by which EPAS1 might trigger pexophagy.