The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation
Open accessAbstract
Peroxisomes are metabolic organelles necessary for anabolic and catabolic lipid reactions whose numbers are highly dynamic based on the metabolic need of the cells. One mechanism to regulate peroxisome numbers is through an autophagic process called pexophagy. In mammalian cells, ubiquitination of peroxisomal membrane proteins signals pexophagy; however, the E3 ligase responsible for mediating ubiquitination is not known. Here, we report that the peroxisomal E3 ubiquitin ligase peroxin 2 (PEX2) is the causative agent for mammalian pexophagy. Expression of PEX2 leads to gross ubiquitination of peroxisomes and degradation of peroxisomes in an NBR1-dependent autophagic process. We identify PEX5 and PMP70 as substrates of PEX2 that are ubiquitinated during amino acid starvation. We also find that PEX2 expression is up-regulated during both amino acid starvation and rapamycin treatment, suggesting that the mTORC1 pathway regulates pexophagy by regulating PEX2 expression levels. Finally, we validate our findings in vivo using an animal model.
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Cites
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
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Self-citationThe role of autophagy during the early neonatal starvation period
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“During peroxisome biogenesis, PEX2 is required to ubiquitinate the membrane-bound form of the matrix protein receptor PEX5 in order for it to be removed from the membrane (Okumoto et al., 1997; Matsumura et al., 2000; Shimura et al., 2000; Platta et al., 2007; Prestele et al., 2010).”
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Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy
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Cited by
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Cargo recognition and degradation by selective autophagy
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Anding, A. L., & Baehrecke, E. H. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.02.016 · Cited by 576
Metadata
- Authors
- Sargent, G., van Zutphen, T., Shatseva, T., Zhang, L., Di Giovanni, V., Bandsma, R., & Kim, P. K.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2016-09-05
- Volume
- 214
- Issue
- 6
- Pages
- 677-690
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2517875366
- Cited by
- 180
- References
- 11
- FWCI
- 16.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Sargent, G., van Zutphen, T., Shatseva, T., Zhang, L., Di Giovanni, V., Bandsma, R., & Kim, P. K. (2016). PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation. Journal of Cell Biology. https://doi.org/10.1083/jcb.201511034
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