Evidence map›Paper›PMID 28655770›Full record

ArticleThe Journal of biological chemistry2017

Phosphorylation of p62 by AMP-activated protein kinase mediates autophagic cell death in adult hippocampal neural stem cells.

Shinwon Ha, Seol-Hwa Jeong, Kyungrim Yi, Kyung Min Chung, Caroline Jeeyeon Hong, Seong Who Kim, Eun-Kyoung Kim, Seong-Woon Yu

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Lipophagy and lipid droplets in neurodegeneration.Trends in pharmacological sciences · 2026
    Review
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  6. Article
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  17. Review
  18. The Dawn of Mitophagy: What Do We Know by Now?Current neuropharmacology · 2021
    Review
  19. Article
  20. p62: Friend or Foe? Evidences forInternational journal of molecular sciences · 2020
    Review
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

8 authors at 3 institutions in 2 countries.

Shinwon HaFrom the Department of Brain and Cognitive Sciences and.
Seol-Hwa JeongFrom the Department of Brain and Cognitive Sciences and.
Kyungrim YiFrom the Department of Brain and Cognitive Sciences and.
Kyung Min ChungFrom the Department of Brain and Cognitive Sciences and.
Caroline Jeeyeon HongFrom the Department of Brain and Cognitive Sciences and.
Seong Who Kimthe Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Eun-Kyoung KimFrom the Department of Brain and Cognitive Sciences and.
Seong-Woon YuFrom the Department of Brain and Cognitive Sciences and yusw@dgist.ac.kr.
Institute of Cognitive and Brain Sciences · USDaegu Gyeongbuk Institute of Science and Technology · KRUlsan College · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the adult brain, programmed death of neural stem cells is considered to be critical for tissue homeostasis and cognitive function and is dysregulated in neurodegeneration. Previously, we have reported that adult rat hippocampal neural (HCN) stem cells undergo autophagic cell death (ACD) following insulin withdrawal. Because the apoptotic capability of the HCN cells was intact, our findings suggested activation of unique molecular mechanisms linking insulin withdrawal to ACD rather than apoptosis. Here, we report that phosphorylation of autophagy-associated protein p62 by AMP-activated protein kinase (AMPK) drives ACD and mitophagy in HCN cells. Pharmacological inhibition of AMPK or genetic ablation of the AMPK α2 subunit by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing suppressed ACD, whereas AMPK activation promoted ACD in insulin-deprived HCN cells. We found that following insulin withdrawal AMPK phosphorylated p62 at a novel site, Ser-293/Ser-294 (in rat and human p62, respectively). Phosphorylated p62 translocated to mitochondria and induced mitophagy and ACD. Interestingly, p62 phosphorylation at Ser-293 was not required for staurosporine-induced apoptosis in HCN cells. To the best of our knowledge, this is the first report on the direct phosphorylation of p62 by AMPK. Our data suggest that AMPK-mediated p62 phosphorylation is an ACD-specific signaling event and provide novel mechanistic insight into the molecular mechanisms in ACD.

Indexed as

AutophagyProtein Processing, Post-TranslationalAdult Stem CellsAmino Acid SubstitutionAMP-Activated Protein KinasesAnimalsAutophagy-Related Protein 7Cells, CulturedCell SurvivalEnzyme ActivationGene DeletionHippocampusHumansNerve Tissue ProteinsNeural Stem CellsPhosphorylationAMP-Activated Protein KinasesAtg7 protein, ratAutophagy-Related Protein 7Nerve Tissue ProteinsProtein Kinase InhibitorsRecombinant Fusion ProteinsSequestosome-1 ProteinSQSTM1 protein, humanSqstm1 protein, ratAMP-activated kinase (AMPK)autophagymitophagyp62 (sequestosome 1 (SQSTM1))phosphorylation

Identifiers

PMID28655770
PMCPMC5566532
OpenAlexW2724886670

What OpenQuestion holds

Textmetadata
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.