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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...

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Detalles Bibliográficos
Autores principales: Yu, Houqing, Kamber, Roarke A, Denic, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000956/
https://www.ncbi.nlm.nih.gov/pubmed/35404228
http://dx.doi.org/10.7554/eLife.74531
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author Yu, Houqing
Kamber, Roarke A
Denic, Vladimir
author_facet Yu, Houqing
Kamber, Roarke A
Denic, Vladimir
author_sort Yu, Houqing
collection PubMed
description 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.
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spelling pubmed-90009562022-04-12 The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast Yu, Houqing Kamber, Roarke A Denic, Vladimir eLife Cell Biology 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. eLife Sciences Publications, Ltd 2022-04-11 /pmc/articles/PMC9000956/ /pubmed/35404228 http://dx.doi.org/10.7554/eLife.74531 Text en © 2022, Yu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Yu, Houqing
Kamber, Roarke A
Denic, Vladimir
The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast
title The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast
title_full The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast
title_fullStr The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast
title_full_unstemmed The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast
title_short The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor Atg36 to suppress pexophagy in yeast
title_sort peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor atg36 to suppress pexophagy in yeast
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000956/
https://www.ncbi.nlm.nih.gov/pubmed/35404228
http://dx.doi.org/10.7554/eLife.74531
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