Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy
| Autor: | Nicholas D. Demers, Derrick Cheng, Rong Hua, Yuqing Wang, G. Angus McQuibban, Peter K. Kim, Amy Wong Strilchuk, Victoria Riccio, Miluska Vissa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Regulator
Peroxisomal Biogenesis Factor 2 medicine.disease_cause Deubiquitinating enzyme Mitochondrial Proteins 03 medical and health sciences Mice 0302 clinical medicine Stress Physiological Report Organelle Mitophagy Chlorocebus aethiops Macroautophagy medicine Autophagy Peroxisomes Animals Humans Research Articles 030304 developmental biology 0303 health sciences Mutation biology Ubiquitination Cell Biology Peroxisome 3. Good health Ubiquitin ligase Cell biology COS Cells biology.protein Commentary Thiolester Hydrolases 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | The Journal of Cell Biology Autophagy |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | The regulation of organelle abundance is crucial for cellular health and function. In this study, Riccio et al. show that the mitochondrial deubiquitinase USP30 localizes to peroxisomes, where it regulates PEX2-dependent pexophagy potential and demonstrates its potential as a therapeutic target for the treatment of Zellweger’s spectrum disorders. The regulation of organelle abundance is critical for cell function and survival; however, the mechanisms responsible are not fully understood. In this study, we characterize a role of the deubiquitinating enzyme USP30 in peroxisome maintenance. Peroxisomes are highly dynamic, changing in abundance in response to metabolic stress. In our recent study identifying the role of USP30 in mitophagy, we observed USP30 to be localized to punctate structures resembling peroxisomes. We report here that USP30, best known as a mitophagy regulator, is also necessary for regulating pexophagy, the selective autophagic degradation of peroxisomes. We find that overexpressing USP30 prevents pexophagy during amino acid starvation, and its depletion results in pexophagy induction under basal conditions. We demonstrate that USP30 prevents pexophagy by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2. Finally, we show that USP30 can rescue the peroxisome loss observed in some disease-causing peroxisome mutations, pointing to a potential therapeutic target. |
| Databáze: | OpenAIRE |
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