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Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes

Peroxisome abundance is regulated by homeostasis between the peroxisomal biogenesis and degradation processes. Peroxin 16 (PEX16) is a peroxisomal protein involved in trafficking membrane proteins for de novo peroxisome biogenesis. The present study demonstrates that PEX16 also modulates peroxisome...

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Autores principales: Wei, Xiaofan, Maharjan, Yunash, Dorotea, Debra, Dutta, Raghbendra-Kumar, Kim, Donghyun, Kim, Hyunsoo, Mu, Yizhu, Park, Channy, Park, Raekil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348608/
https://www.ncbi.nlm.nih.gov/pubmed/34360754
http://dx.doi.org/10.3390/ijms22157989
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author Wei, Xiaofan
Maharjan, Yunash
Dorotea, Debra
Dutta, Raghbendra-Kumar
Kim, Donghyun
Kim, Hyunsoo
Mu, Yizhu
Park, Channy
Park, Raekil
author_facet Wei, Xiaofan
Maharjan, Yunash
Dorotea, Debra
Dutta, Raghbendra-Kumar
Kim, Donghyun
Kim, Hyunsoo
Mu, Yizhu
Park, Channy
Park, Raekil
author_sort Wei, Xiaofan
collection PubMed
description Peroxisome abundance is regulated by homeostasis between the peroxisomal biogenesis and degradation processes. Peroxin 16 (PEX16) is a peroxisomal protein involved in trafficking membrane proteins for de novo peroxisome biogenesis. The present study demonstrates that PEX16 also modulates peroxisome abundance through pexophagic degradation. PEX16 knockdown in human retinal pigment epithelial-1 cells decreased peroxisome abundance and function, represented by reductions in the expression of peroxisome membrane protein ABCD3 and the levels of cholesterol and plasmalogens, respectively. The activation of pexophagy under PEX16 knockdown was shown by (i) abrogated peroxisome loss under PEX16 knockdown in autophagy-deficient ATG5 knockout cell lines, and (ii) increased autophagy flux and co-localization of p62—an autophagy adaptor protein—with ABCD3 in the presence of the autophagy inhibitor chloroquine. However, the levels of cholesterol and plasmalogens did not recover despite the restoration of peroxisome abundance following chloroquine treatment. Thus, PEX16 is indispensable for maintaining peroxisome homeostasis by regulating not only the commonly known biogenesis pathway but also the autophagic degradation of peroxisomes.
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spelling pubmed-83486082021-08-08 Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes Wei, Xiaofan Maharjan, Yunash Dorotea, Debra Dutta, Raghbendra-Kumar Kim, Donghyun Kim, Hyunsoo Mu, Yizhu Park, Channy Park, Raekil Int J Mol Sci Article Peroxisome abundance is regulated by homeostasis between the peroxisomal biogenesis and degradation processes. Peroxin 16 (PEX16) is a peroxisomal protein involved in trafficking membrane proteins for de novo peroxisome biogenesis. The present study demonstrates that PEX16 also modulates peroxisome abundance through pexophagic degradation. PEX16 knockdown in human retinal pigment epithelial-1 cells decreased peroxisome abundance and function, represented by reductions in the expression of peroxisome membrane protein ABCD3 and the levels of cholesterol and plasmalogens, respectively. The activation of pexophagy under PEX16 knockdown was shown by (i) abrogated peroxisome loss under PEX16 knockdown in autophagy-deficient ATG5 knockout cell lines, and (ii) increased autophagy flux and co-localization of p62—an autophagy adaptor protein—with ABCD3 in the presence of the autophagy inhibitor chloroquine. However, the levels of cholesterol and plasmalogens did not recover despite the restoration of peroxisome abundance following chloroquine treatment. Thus, PEX16 is indispensable for maintaining peroxisome homeostasis by regulating not only the commonly known biogenesis pathway but also the autophagic degradation of peroxisomes. MDPI 2021-07-26 /pmc/articles/PMC8348608/ /pubmed/34360754 http://dx.doi.org/10.3390/ijms22157989 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wei, Xiaofan
Maharjan, Yunash
Dorotea, Debra
Dutta, Raghbendra-Kumar
Kim, Donghyun
Kim, Hyunsoo
Mu, Yizhu
Park, Channy
Park, Raekil
Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes
title Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes
title_full Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes
title_fullStr Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes
title_full_unstemmed Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes
title_short Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes
title_sort knockdown of pex16 induces autophagic degradation of peroxisomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348608/
https://www.ncbi.nlm.nih.gov/pubmed/34360754
http://dx.doi.org/10.3390/ijms22157989
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