The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast

Autophagy receptor (or adaptor) proteins facilitate lysosomal destruction of various organelles in response to cellular stress, including nutrient deprivation. To what extent membrane-resident autophagy receptors also respond to organelle-restricted cues to induce selective autophagy remains poorly understood. We find that latent activation of the yeast pexophagy receptor Atg36 by the casein kinase Hrr25 in rich media is repressed by the ATPase activity of Pex1/6, the catalytic subunits of the exportomer AAA+ transmembrane complex enabling protein import into peroxisomes. Quantitative proteomics of purified Pex3, an obligate Atg36 coreceptor, support a model in which the exportomer tail anchored to the peroxisome membrane represses Atg36 phosphorylation on Pex3 without assistance from additional membrane factors. Indeed, we reconstitute inhibition of Atg36 phosphorylation in vitro using soluble Pex1/6 and define an N-terminal unstructured region of Atg36 that enables regulation by binding to Pex1. Our findings uncover a mechanism by which a compartment-specific AAA+ complex mediating organelle biogenesis and protein quality control staves off induction of selective autophagy.

Automated summary

Autophagy receptor proteins facilitate the destruction of organelles in response to cellular stress. However, the mechanism by which membrane-resident autophagy receptors induce selective autophagy in response to organelle-restricted signals is poorly understood. This study reveals that the ATPase activity of the Pex1/6 complex represses the activation of the pexophagy receptor Atg36 by the casein kinase Hrr25 in yeast cells. In addition, the study identifies a mechanism in which the exportomer complex represses the phosphorylation of Atg36 on Pex3 without the assistance of additional membrane factors. This mechanism prevents the induction of selective autophagy and provides insights into the regulation of organelle homeostasis.