Loss of HSPA9 induces peroxisomal degradation by increasing pexophagy

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Title
Loss of HSPA9 induces peroxisomal degradation by increasing pexophagy
Author(s)
D S Jo; S J Park; Ae-Kyeong Kim; N Y Park; J B Kim; J E Bae; H J Park; J H Shin; J W Chang; P K Kim; Y K Jung; J Y Koh; S K Choe; Kyu-Sun Lee; D H Cho
Bibliographic Citation
Autophagy, vol. 16, no. 11, pp. 1989-2003
Publication Year
2020
Abstract
Quality control of peroxisomes is essential for cellular homeostasis. However, the mechanism underlying pexophagy is largely unknown. In this study, we identified HSPA9 as a novel pexophagy regulator. Downregulation of HSPA9 increased macroautophagy/autophagy but decreased the number of peroxisomes in vitro and in vivo. The loss of peroxisomes by HSPA9 depletion was attenuated in SQSTM1-deficient cells. In HSPA9-deficient cells, the level of peroxisomal reactive oxygen species (ROS) increased, while inhibition of ROS blocked pexophagy in HeLa and SH-SY5Y cells. Importantly, reconstitution of HSPA9 mutants found in Parkinson disease failed to rescue the loss of peroxisomes, whereas reconstitution with wild type inhibited pexophagy in HSPA9-depleted cells. Knockdown of Hsc70-5 decreased peroxisomes in Drosophila, and the HSPA9 mutants failed to rescue the loss of peroxisomes in Hsc70-5-depleted flies. Taken together, our findings suggest that the loss of HSPA9 enhances peroxisomal degradation by pexophagy.
Keyword
DrosophilaHSPA9Parkinson diseaseperoxisomepexophagyROS
ISSN
1554-8627
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.1080/15548627.2020.1712812
Type
Article
Appears in Collections:
Division of Research on National Challenges > Bionanotechnology Research Center > 1. Journal Articles
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