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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8348608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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