Evidence map›Paper›PMID 31949499›Full record

ArticleJournal of Cancer2020

Pyruvate dehydrogenase kinase 1 interferes with glucose metabolism reprogramming and mitochondrial quality control to aggravate stress damage in cancer.

Xinyue Deng, Quan Wang, Meiyu Cheng, Yingying Chen, Xiaoyu Yan, Rui Guo, Liankun Sun, Yang Li, Yanan Liu

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

Article in Journal of Cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
0.7field-weighted citation impact, top 35% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
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  13. Mitochondrial dysfunction, UPRCell & bioscience · 2021
    Review
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  17. Oxidative medicine and cellular longevity · 2021
    Article
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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.

Xinyue DengDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Quan WangDepartment of Radiation Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
Meiyu ChengDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Yingying ChenDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Xiaoyu YanDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Rui GuoDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Liankun SunDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Yang LiDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Yanan LiuDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Jilin University · CNJilin Medical University · CNUnion Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pyruvate dehydrogenase kinase 1 (PDK1) is a key factor in the connection between glycolysis and the tricarboxylic acid cycle. Restoring the mitochondrial OXPHOS function by inhibiting glycolysis through targeting PDK1 has become a hot spot for tumor therapy. However, the specific mechanism by which metabolic changes affect mitochondrial function remains unclear. Recent studies have found that mitochondrial quality control such as mitochondrial protein homeostasis plays an important role in maintaining mitochondrial function. Here, we focused on PDK1 and explored the specific mechanism by which metabolic changes affect mitochondrial OXPHOS function. We showed that glucose metabolism in HepG2 and HepG3B cells switched from anaerobic glycolysis to the mitochondrial tricarboxylic acid cycle under different concentrations of dichloroacetate (DCA) or short hairpin PDK1. After DCA treatment or knockdown of PDK1, the mitochondrial morphology was gradually condensed and exhibited shorter and more fragmented filaments. Additionally, expression of the mitochondrial autophagy proteins parkin and PTEN-induced kinase was down-regulated, and the biosynthetic protein peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and its regulated complex I, III, IV, and V protein were down-regulated. This indicated that PDK1 inhibition affected the level of mitochondrial quality control. Analysis of mitochondrial function revealed significantly increased mitochondrial reactive oxygen species and decreased membrane potential. Therefore, glucose metabolism reprogramming by PDK1 inhibition could induce mitochondrial quality control disorders to aggravate mitochondrial stress damage.

Indexed as

DCAglucose metabolic reprogrammingmitochondiral quality controloxidative phosphorylationPDK1.

Identifiers

PMID31949499
PMCPMC6959030
OpenAlexW3004542377

What OpenQuestion holds

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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.