In vitro study demonstrates that Pex14 phosphorylation inhibits peroxisomal catalase import during oxidative stress in mammalian cells, suggesting a protective cytosolic mechanism.
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. The H 2 O 2 -induced phosphorylation of Pex14 at Ser232 suppresses peroxisomal import of catalase in vivo and selectively impairs in vitro the interaction of catalase with the Pex14-Pex5 complex. A phosphomimetic mutant Pex14-S232D elevates the level of cytosolic catalase, but not canonical PTS1-proteins, conferring higher cell resistance to H 2 O 2 . We thus suggest that the 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.
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Okumoto et al. (2020) studied this question.
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