Evidence map›Paper›PMID 33465003›Full record

ArticleAutophagy2021

Autophagy restricts mitochondrial DNA damage-induced release of ENDOG (endonuclease G) to regulate genome stability.

Tung Chao, Hsueh-Tzu Shih, Shih-Chin Hsu, Pei-Jer Chen, Yu-Shan Fan, Yung-Ming Jeng, Zhao-Qing Shen, Ting-Fen Tsai, Zee-Fen Chang

Open access · greenAbstract read
In one paragraph

Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

31 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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  5. Review
  6. Article
  7. Article
  8. Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025
    Review
  9. Article
  10. Review
  11. Evaluation of the safety and efficacy ofFrontiers in immunology · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023
    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

9 authors at 3 institutions in 1 country.

Tung ChaoInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsueh-Tzu ShihInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Shih-Chin HsuInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Pei-Jer ChenCenter of Precision Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yu-Shan FanInstitute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yung-Ming JengDepartment of Pathology, National Taiwan University, Hospital, Taipei, Taiwan.
Zhao-Qing ShenDepartment of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
Ting-Fen TsaiDepartment of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
Zee-Fen ChangInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
National Taiwan University · TWNational Taiwan University Hospital · TWNational Yang Ming Chiao Tung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genotoxic insult causes nuclear and mitochondrial DNA damages with macroautophagy/autophagy induction. The role of mitochondrial DNA (mtDNA) damage in the requirement of autophagy for nuclear DNA (nDNA) stability is unclear. Using site-specific DNA damage approaches, we show that specific nDNA damage alone does not require autophagy for repair unless in the presence of mtDNA damage. We provide evidence that after IR exposure-induced mtDNA and nDNA damages, autophagy suppression causes non-apoptotic mitochondrial permeability, by which mitochondrial ENDOG (endonuclease G) is released and translocated to nuclei to sustain nDNA damage in a TET (tet methylcytosine dioxygenase)-dependent manner. Furthermore, blocking lysosome function is sufficient to increase the amount of mtDNA leakage to the cytosol, accompanied by ENDOG-free mitochondrial puncta formation with concurrent ENDOG nuclear accumulation. We proposed that autophagy eliminates the mitochondria specified by mtDNA damage-driven mitochondrial permeability to prevent ENDOG-mediated genome instability. Finally, we showed that HBx, a hepatitis B viral protein capable of suppressing autophagy, also causes mitochondrial permeability-dependent ENDOG mis-localization in nuclei and is linked to hepatitis B virus (HBV)-mediated hepatocellular carcinoma development.

Indexed as

DNA DamageGenomic InstabilityActive Transport, Cell NucleusAutophagyCarcinoma, HepatocellularCell Line, TumorDioxygenasesDNA-Binding ProteinsDNA, MitochondrialEndodeoxyribonucleasesGene Knockdown TechniquesHeLa CellsHumansLiver NeoplasmsMitochondriaPermeabilityDioxygenasesDNA-Binding ProteinsDNA, MitochondrialEndodeoxyribonucleasesendonuclease GTET2 protein, humanAutophagyendonuclease Ggenome instabilitymitochondrial DNAmitochondrial permeabilityTET

Identifiers

PMID33465003
PMCPMC8632313
OpenAlexW3125770673

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.