PUBLICATION
PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS
- Authors
- Demers, N.D., Riccio, V., Jo, D.S., Bhandari, S., Law, K.B., Liao, W., Kim, C., McQuibban, G.A., Choe, S.K., Cho, D.H., Kim, P.K.
- ID
- ZDB-PUB-221222-4
- Date
- 2022
- Source
- Autophagy 19(6): 1781-1802 (Journal)
- Registered Authors
- Bhandari, Sushil, Choe, Seong-Kyu
- Keywords
- PEX13, PEX5, Peroxisomes, pexophagy, reactive oxygen species, selective autophagy, ubiquitin, zebrafish
- MeSH Terms
-
- Actins/metabolism
- Amino Acids/metabolism
- Animals
- Autophagy*/physiology
- Fibroblasts/metabolism
- Humans
- Leucine/metabolism
- Lysine/metabolism
- Macroautophagy*
- Membrane Proteins/metabolism
- Mice
- Oxygen/metabolism
- Peroxisomes/metabolism
- Reactive Oxygen Species/metabolism
- Sirolimus
- Ubiquitin/metabolism
- Zebrafish/metabolism
- PubMed
- 36541703 Full text @ Autophagy
Citation
Demers, N.D., Riccio, V., Jo, D.S., Bhandari, S., Law, K.B., Liao, W., Kim, C., McQuibban, G.A., Choe, S.K., Cho, D.H., Kim, P.K. (2022) PEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS. Autophagy. 19(6):1781-1802.
Abstract
Peroxisomes are rapidly degraded during amino acid and oxygen deprivation by a type of selective autophagy called pexophagy. However, how damaged peroxisomes are detected and removed from the cell is poorly understood. Recent studies suggest that the peroxisomal matrix protein import machinery may serve double duty as a quality control machinery, where they are directly involved in activating pexophagy. Here, we explored whether any matrix import factors are required to prevent pexophagy, such that their loss designates peroxisomes for degradation. Using gene editing and quantitative fluorescence microscopy on culture cells and a zebrafish model system, we found that PEX13, a component of the peroxisomal matrix import system, is required to prevent the degradation of otherwise healthy peroxisomes. The loss of PEX13 caused an accumulation of ubiquitinated PEX5 on peroxisomes and an increase in peroxisome-dependent reactive oxygen species that coalesce to induce pexophagy. We also found that PEX13 protein level is downregulated to aid in the induction of pexophagy during amino acid starvation. Together, our study points to PEX13 as a novel pexophagy regulator that is modulated to maintain peroxisome homeostasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping