Evidence map›Paper›PMID 27597759›Full record

ArticleThe Journal of cell biology2016

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

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 2 pooled it
14.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 175 citations in OpenAlex.

  1. Pooled it
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  4. Article
  5. Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
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  20. AAA+ ATPase chaperone p97/VCPNature communications · 2024
    Article

48 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Graeme SargentCell Biology Department, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada Biochemistry Department, University of Toronto, Toronto, ON M5S 1A8, Canada.
Tim van ZutphenDepartment of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, 9700 AD Groningen, Netherlands.
Tatiana ShatsevaBiochemistry Department, University of Toronto, Toronto, ON M5S 1A8, Canada.
Ling ZhangPhysiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Valeria Di GiovanniPhysiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Robert BandsmaDepartment of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada Physiology and Experimental Medicine Program, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada pkim@sickkids.ca robert.bandsma@sickkids.ca.
Peter Kijun KimCell Biology Department, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada Biochemistry Department, University of Toronto, Toronto, ON M5S 1A8, Canada.ORCID 0000-0001-6626-0575
Hospital for Sick Children · CAUniversity of Toronto · CAUniversity Medical Center Groningen · NL

Funding

CIHR
6 · The paper itself

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.

Indexed as

AutophagyAmino AcidsAnimalsATP-Binding Cassette TransportersDisease Models, AnimalHEK293 CellsHeLa CellsHumansIntracellular Signaling Peptides and ProteinsMaleMechanistic Target of Rapamycin Complex 1Membrane ProteinsMice, Inbred C57BLMultiprotein ComplexesPeroxisomal Biogenesis Factor 2PeroxisomesABCD3 protein, humanAbcd3 protein, mouseAmino AcidsATP-Binding Cassette TransportersIntracellular Signaling Peptides and ProteinsMechanistic Target of Rapamycin Complex 1Membrane ProteinsMTOR protein, humanMultiprotein ComplexesNBR1 protein, humanPeroxisomal Biogenesis Factor 2Peroxisome-Targeting Signal 1 ReceptorPEX2 protein, humanPEX2 protein, mousePex2 protein, ratPEX5 protein, humanPex5 protein, mouseProteinsReceptors, Cytoplasmic and NuclearSirolimusTOR Serine-Threonine Kinases

Identifiers

PMID27597759
PMCPMC5021090
OpenAlexW2517875366

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.