Peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation

Most of peroxisomal matrix proteins including a hydrogen peroxide (H ₂ O ₂ )-decomposing enzyme, catalase, are imported in a peroxisome-targeting signal type-1 (PTS1)-dependent manner. However, little is known about regulation of the membrane-bound protein import machinery. Here, we report that Pex14, a central component of the protein translocation complex in peroxisomal membrane, is phosphorylated in response to oxidative stresses such as H ₂ O ₂ in mammalian cells. H ₂ O ₂ -induced phosphorylation of Pex14 at Ser232 suppresses peroxisomal import of catalase in vivo and selectively decreases formation of PTS1 receptor Pex5-mediated ternary complex of Pex14 with catalase in vitro . Phosphomimetic Pex14-S232D mutant elevates the level of cytosolic catalase, but not canonical PTS1-proteins, conferring higher cell resistance to H ₂ O ₂ . We thus suggest that H ₂ O ₂ -induced phosphorylation of Pex14 spatiotemporally regulates peroxisomal import of catalase, functioning in counteracting action against oxidative stress by the increase of cytosolic catalase.