ArticlePloS one2015
Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Mitochondrial NADH-redox inflexibility constrains genomic and epigenetic stability in pluripotent stem cells.The EMBO journal · 2026Article
- Metabolic regulation of T cell production of IL-10 and IL-22 protects against intestinal inflammation.Precision clinical medicine · 2025Article
- p53 Orchestrates Cancer Metabolism: Unveiling Strategies to Reverse the Warburg Effect.Bulletin of mathematical biology · 2024Article
- The Key Role of Mitochondria in Somatic Stem Cell Differentiation: From Mitochondrial Asymmetric Apportioning to Cell Fate.International journal of molecular sciences · 2023Review
- Metabolic control of induced pluripotency.Frontiers in cell and developmental biology · 2023Review
- Regulation of cleavage embryo genes upon DRP1 inhibition in mouse embryonic stem cells.Frontiers in cell and developmental biology · 2023Article
- Leucine and Arginine Availability Modulate Mouse Embryonic Stem Cell Proliferation and Metabolism.International journal of molecular sciences · 2022Article
- Differential Oxygen Exposure Modulates Mesenchymal Stem Cell Metabolism and Proliferation through mTOR Signaling.International journal of molecular sciences · 2022Article
- Glycolytic Profiling of Mouse Embryonic Stem Cells (mESCs).Methods in molecular biology (Clifton, N.J.) · 2022Article
- Chromatin as a sensor of metabolic changes during early development.Frontiers in cell and developmental biology · 2022Review
- Nutrients in the fate of pluripotent stem cells.Cell metabolism · 2021Review
- Chimeric Drug Design with a Noncharged Carrier for Mitochondrial Delivery.Pharmaceutics · 2021Article
- Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate Improves Host Control ofFrontiers in immunology · 2021Article
- Effects of DMSO on the Pluripotency of Cultured Mouse Embryonic Stem Cells (mESCs).Stem cells international · 2020Article
- The Metabolic Interplay between Cancer and Other Diseases.Trends in cancer · 2019Review
- Elevated Exogenous Pyruvate Potentiates Mesodermal Differentiation through Metabolic Modulation and AMPK/mTOR Pathway in Human Embryonic Stem Cells.Stem cell reports · 2019Article
- Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications.Oxidative medicine and cellular longevity · 2019Review
- Two dichloric compounds inhibit in vivo U87 xenograft tumor growth.Cancer biology & therapy · 2019Article
- Biological Significance of the Suppression of Oxidative Phosphorylation in Induced Pluripotent Stem Cells.Cell reports · 2017Article
- Data on the potential impact of food supplements on the growth of mouse embryonic stem cells.Data in brief · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe pyruvate dehydrogenase (PDH) complex is localized in the mitochondrial matrix catalyzing the irreversible decarboxylation of pyruvate to acetyl-CoA and NADH. For proper complex regulation the E1-α subunit functions as an on/off switch regulated by phosphorylation/dephosphorylation. In different cell types one of the four-pyruvate dehydrogenase kinase isoforms (PDHK1-4) can phosphorylate this subunit leading to PDH inactivation. Our previous results with human Embryonic Stem Cells (hESC), suggested that PDHK could be a key regulator in the metabolic profile of pluripotent cells, as it is upregulated in pluripotent stem cells. Therefore, we wondered if metabolic modulation, via inexpensive pharmacological inhibition of PDHK, could impact metabolism and pluripotency. METHODS/
resultsIn order to assess the importance of the PDH cycle in mouse Embryonic Stem Cells (mESC), we incubated cells with the PDHK inhibitor dichloroacetate (DCA) and observed that in its presence ESC started to differentiate. Changes in mitochondrial function and proliferation potential were also found and protein levels for PDH (both phosphorylated and non-phosphorylated) and PDHK1 were monitored. Interestingly, we were also able to describe a possible pathway that involves Hif-1α and p53 during DCA-induced loss of pluripotency. Results with ESCs treated with DCA were comparable to those obtained for cells grown without Leukemia Inhibitor Factor (LIF), used in this case as a positive control for differentiation.
conclusionsDCA negatively affects ESC pluripotency by changing cell metabolism and elements related to the PDH cycle, suggesting that PDHK could function as a possible metabolic gatekeeper in ESC, and may be a good target to modulate metabolism and differentiation. Although further molecular biology-based experiments are required, our data suggests that inactive PDH favors pluripotency and that ESC have similar strategies as cancer cells to maintain a glycolytic profile, by using some of the signaling pathways found in the latter cells.
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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.