Evidence map›Paper›PMID 30658448›Full record

ArticleCells2019

Oxidative Insults and Mitochondrial DNA Mutation Promote Enhanced Autophagy and Mitophagy Compromising Cell Viability in Pluripotent Cell Model of Mitochondrial Disease.

Dar-Shong Lin, Yu-Wen Huang, Che-Sheng Ho, Pi-Lien Hung, Mei-Hsin Hsu, Tuan-Jen Wang, Tsu-Yen Wu, Tsung-Han Lee, Zo-Darr Huang, Po-Chun Chang and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
6.5field-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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Dl-3-ACS chemical neuroscience · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. 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

11 authors at 5 institutions in 1 country.

Dar-Shong LinDepartment of Pediatrics, Mackay Memorial Hospital, Taipei 10449, Taiwan. lin.ds.md@gmail.com.
Yu-Wen HuangDepartment of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan. wendyhuang1219@gmail.com.
Che-Sheng HoDepartment of Pediatrics, Mackay Memorial Hospital, Taipei 10449, Taiwan. pedcsho@gmail.com.
Pi-Lien HungDepartment of Pediatric Neurology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 88301, Taiwan. flora1402@cgmh.org.tw.
Mei-Hsin HsuDepartment of Pediatric Neurology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung 88301, Taiwan. a03peggy@cgmh.org.tw.
Tuan-Jen WangDepartment of Laboratory Medicine, Mackay Memorial Hospital, Taipei 10449, Taiwan. dj.wang@mmh.org.tw.
Tsu-Yen WuDepartment of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan. linws@mmh.org.tw.
Tsung-Han LeeDepartment of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan. randy.b746mmh@gmail.com.
Zo-Darr HuangDepartment of Medical Research, Mackay Memorial Hospital, Taipei 10449, Taiwan. darr.9475@mmh.org.tw.
Po-Chun ChangDepartment of Information Technology, Mackay Memorial Hospital, Taipei 10449, Taiwan. f1481101@gmail.com.
Ming-Fu ChiangDepartment of Neurosurgery, Mackay Memorial Hospital, Taipei 10449, Taiwan. chiang66@gmail.com.
Mackay Memorial Hospital · TWChang Gung University · TWKaohsiung Chang Gung Memorial Hospital · TWMackay Medical College · TWTaipei Medical University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysfunction of mitochondria causes defects in oxidative phosphorylation system (OXPHOS) and increased production of reactive oxygen species (ROS) triggering the activation of the cell death pathway that underlies the pathogenesis of aging and various diseases. The process of autophagy to degrade damaged cytoplasmic components as well as dysfunctional mitochondria is essential for ensuring cell survival. We analyzed the role of autophagy inpatient-specific induced pluripotent stem (iPS) cells generated from fibroblasts of patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with well-characterized mitochondrial DNA mutations and distinct OXPHOS defects. MELAS iPS cells recapitulated the pathogenesis of MELAS syndrome, and showed an increase of autophagy in comparison with its isogenic normal counterpart, whereas mitophagy is very scarce at the basal condition. Our results indicated that the existence of pathogenic mtDNA alone in mitochondrial disease was not sufficient to elicit the degradation of dysfunctional mitochondria. Nonetheless, oxidative insults induced bulk macroautophagy with the accumulation of autophagosomes and autolysosomes upon marked elevation of ROS, overload of intracellular calcium, and robust depolarization of mitochondrial membrane potential, while mitochondria respiratory function was impaired and widespread mitophagy compromised cell viability. Collectively, our studies provide insights into the dysfunction of autophagy and activation of mitophagy contributing to the pathological mechanism of mitochondrial disease.

Indexed as

Models, BiologicalAdenosine TriphosphateAutophagosomesAutophagyBiomarkersCalciumCell MembraneCell RespirationCell SurvivalCytoplasmDNA, MitochondrialEnergy MetabolismFibroblastsHumansInduced Pluripotent Stem CellsLysosomesAdenosine TriphosphateBiomarkersCalciumDNA, MitochondrialReactive Oxygen SpeciesautophagyiPS cellsMELASmitochondrial diseasesmitophagy

Identifiers

PMID30658448
PMCPMC6356288
OpenAlexW2909224188

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.