Selenoprotein dio2 is a regulator of mitochondrial function, morphology and uprmt in human cardiomyocytes
| Autor: | Eugene Berezikov, Annet N. Linders, Herman H W Silljé, Peter van der Meer, Warner S. Simonides, Frederik E. Deiman, B. Daan Westenbrink, Mario G. Pavez-Giani, Nils Bomer, Martijn F Hoes, Silke U. Oberdorf-Maass, Christiane L.J. Baierl, Rudolf A. de Boer |
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| Přispěvatelé: | Physiology, ACS - Heart failure & arrhythmias, Cardiovascular Centre (CVC), Stem Cell Aging Leukemia and Lymphoma (SALL), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pluripotent Stem Cells
mtUPR QH301-705.5 Deiodinase Regulator DIO2 heart failure Biology Iodide Peroxidase Catalysis Article Inorganic Chemistry Mice mitochondrial function Mitochondrial unfolded protein response Animals Humans Gene silencing fetal-gene-program Myocytes Cardiac Biology (General) Physical and Theoretical Chemistry Induced pluripotent stem cell QD1-999 Molecular Biology Spectroscopy chemistry.chemical_classification Gene knockdown human cardiomyocytes Organic Chemistry General Medicine Mitochondria Computer Science Applications Cell biology Chemistry Fetal‐gene‐program chemistry Unfolded Protein Response biology.protein selenoproteins Selenoprotein |
| Zdroj: | Bomer, N, Pavez-giani, M G, Deiman, F E, Linders, A N, Hoes, M F, Baierl, C L J, Oberdorf-maass, S U, de Boer, R A, Silljé, H H W, Berezikov, E, Simonides, W S, Westenbrink, B D & van der Meer, P 2021, ' Selenoprotein dio2 is a regulator of mitochondrial function, morphology and uprmt in human cardiomyocytes ', International Journal of Molecular Sciences, vol. 22, no. 21, 11906 . https://doi.org/10.3390/ijms222111906 International Journal of Molecular Sciences Volume 22 Issue 21 International Journal of Molecular Sciences, 22(21):11906. Multidisciplinary Digital Publishing Institute (MDPI) International Journal of Molecular Sciences, 22(21):11906. MDPI AG International Journal of Molecular Sciences, Vol 22, Iss 11906, p 11906 (2021) |
| ISSN: | 1661-6596 |
| DOI: | 10.3390/ijms222111906 |
| Popis: | Members of the fetal-gene-program may act as regulatory components to impede deleterious events occurring with cardiac remodeling, and constitute potential novel therapeutic heart failure (HF) targets. Mitochondrial energy derangements occur both during early fetal development and in patients with HF. Here we aim to elucidate the role of DIO2, a member of the fetal-gene-program, in pluripotent stem cell (PSC)-derived human cardiomyocytes and on mitochondrial dynamics and energetics, specifically. RNA sequencing and pathway enrichment analysis was performed on mouse cardiac tissue at different time points during development, adult age, and ischemia-induced HF. To determine the function of DIO2 in cardiomyocytes, a stable human hPSC-line with a DIO2 knockdown was made using a short harpin sequence. Firstly, we showed the selenoprotein, type II deiodinase (DIO2): the enzyme responsible for the tissue-specific conversion of inactive (T4) into active thyroid hormone (T3), to be a member of the fetal-gene-program. Secondly, silencing DIO2 resulted in an increased reactive oxygen species, impaired activation of the mitochondrial unfolded protein response, severely impaired mitochondrial respiration and reduced cellular viability. Microscopical 3D reconstruction of the mitochondrial network displayed substantial mitochondrial fragmentation. Summarizing, we identified DIO2 to be a member of the fetal-gene-program and as a key regulator of mitochondrial performance in human cardiomyocytes. Our results suggest a key position of human DIO2 as a regulator of mitochondrial function in human cardiomyocytes. |
| Databáze: | OpenAIRE |
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