Knockdown of PEX16 Induces Autophagic Degradation of Peroxisomes
| Autor: | Hyun Soo Kim, Yizhu Mu, Raekil Park, Debra Dorotea, Xiaofan Wei, Raghbendra-Kumar Dutta, Yunash Maharjan, Channy Park, Donghyun Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
autophagy QH301-705.5 ATG5 Peroxin PEX16 Retinal Pigment Epithelium Article Catalysis Autophagy-Related Protein 5 Cell Line Inorganic Chemistry chloroquine 03 medical and health sciences 0302 clinical medicine ABCD3 peroxins Humans Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Gene knockdown biology Chemistry Organic Chemistry Autophagy Membrane Proteins peroxisomes General Medicine Peroxisome pexophagy Computer Science Applications Cell biology 030104 developmental biology Membrane protein Gene Knockdown Techniques 030220 oncology & carcinogenesis biology.protein ATP-Binding Cassette Transporters Biogenesis |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 15 International Journal of Molecular Sciences, Vol 22, Iss 7989, p 7989 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22157989 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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