Related Experiment Video
Updated: Mar 15, 2026

Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation
Graeme Sargent1, Tim van Zutphen2, Tatiana Shatseva3
1Cell Biology Department, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada Biochemistry Department, University of Toronto, Toronto, ON M5S 1A8, Canada.
Abstract:
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.
Related Concept Videos
Protein Import into the Peroxisomes
Peroxisomal Protein Import:
Peroxisomes lack the genetic machinery required to code for their own proteins. Hence, most peroxisomal membrane, lumenal and transmembrane proteins are synthesized in the cytoplasm or ER and transported to the peroxisome...
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation
The Unfolded Protein Response
Export of Misfolded Proteins out of the ER
Stringent Response in E. coli

