PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation

Graeme Sargent, Tim van Zutphen, Tatiana Shatseva, Ling Zhang, Valeria Di Giovanni, Robert Bandsma, Peter Kijun Kim

    OnderzoeksoutputAcademicpeer review

    126 Citaten (Scopus)
    383 Downloads (Pure)


    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.

    Originele taal-2English
    Pagina's (van-tot)677-690
    Aantal pagina's14
    TijdschriftThe Journal of Cell Biology
    Nummer van het tijdschrift6
    StatusPublished - 12-sep.-2016

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