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Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes
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| Zeitschriftentitel: | International Journal of Molecular Sciences |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , |
| In: | International Journal of Molecular Sciences, 22, 2021, 21, S. 11906 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
MDPI AG
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| Schlagwörter: |
| author_facet |
Bomer, Nils Pavez-Giani, Mario G. Deiman, Frederik E. Linders, Annet N. Hoes, Martijn F. Baierl, Christiane L.J. Oberdorf-Maass, Silke U. de Boer, Rudolf A. Silljé, Herman H.W. Berezikov, Eugene Simonides, Warner S. Westenbrink, B. Daan van der Meer, Peter Bomer, Nils Pavez-Giani, Mario G. Deiman, Frederik E. Linders, Annet N. Hoes, Martijn F. Baierl, Christiane L.J. Oberdorf-Maass, Silke U. de Boer, Rudolf A. Silljé, Herman H.W. Berezikov, Eugene Simonides, Warner S. Westenbrink, B. Daan van der Meer, Peter |
|---|---|
| author |
Bomer, Nils Pavez-Giani, Mario G. Deiman, Frederik E. Linders, Annet N. Hoes, Martijn F. Baierl, Christiane L.J. Oberdorf-Maass, Silke U. de Boer, Rudolf A. Silljé, Herman H.W. Berezikov, Eugene Simonides, Warner S. Westenbrink, B. Daan van der Meer, Peter |
| spellingShingle |
Bomer, Nils Pavez-Giani, Mario G. Deiman, Frederik E. Linders, Annet N. Hoes, Martijn F. Baierl, Christiane L.J. Oberdorf-Maass, Silke U. de Boer, Rudolf A. Silljé, Herman H.W. Berezikov, Eugene Simonides, Warner S. Westenbrink, B. Daan van der Meer, Peter International Journal of Molecular Sciences Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| author_sort |
bomer, nils |
| spelling |
Bomer, Nils Pavez-Giani, Mario G. Deiman, Frederik E. Linders, Annet N. Hoes, Martijn F. Baierl, Christiane L.J. Oberdorf-Maass, Silke U. de Boer, Rudolf A. Silljé, Herman H.W. Berezikov, Eugene Simonides, Warner S. Westenbrink, B. Daan van der Meer, Peter 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms222111906 <jats:p>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.</jats:p> Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes International Journal of Molecular Sciences |
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| title |
Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_unstemmed |
Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_full |
Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_fullStr |
Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_full_unstemmed |
Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_short |
Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_sort |
selenoprotein dio2 is a regulator of mitochondrial function, morphology and uprmt in human cardiomyocytes |
| topic |
Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
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http://dx.doi.org/10.3390/ijms222111906 |
| publishDate |
2021 |
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11906 |
| description |
<jats:p>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.</jats:p> |
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| author | Bomer, Nils, Pavez-Giani, Mario G., Deiman, Frederik E., Linders, Annet N., Hoes, Martijn F., Baierl, Christiane L.J., Oberdorf-Maass, Silke U., de Boer, Rudolf A., Silljé, Herman H.W., Berezikov, Eugene, Simonides, Warner S., Westenbrink, B. Daan, van der Meer, Peter |
| author_facet | Bomer, Nils, Pavez-Giani, Mario G., Deiman, Frederik E., Linders, Annet N., Hoes, Martijn F., Baierl, Christiane L.J., Oberdorf-Maass, Silke U., de Boer, Rudolf A., Silljé, Herman H.W., Berezikov, Eugene, Simonides, Warner S., Westenbrink, B. Daan, van der Meer, Peter, Bomer, Nils, Pavez-Giani, Mario G., Deiman, Frederik E., Linders, Annet N., Hoes, Martijn F., Baierl, Christiane L.J., Oberdorf-Maass, Silke U., de Boer, Rudolf A., Silljé, Herman H.W., Berezikov, Eugene, Simonides, Warner S., Westenbrink, B. Daan, van der Meer, Peter |
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| description | <jats:p>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.</jats:p> |
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| spelling | Bomer, Nils Pavez-Giani, Mario G. Deiman, Frederik E. Linders, Annet N. Hoes, Martijn F. Baierl, Christiane L.J. Oberdorf-Maass, Silke U. de Boer, Rudolf A. Silljé, Herman H.W. Berezikov, Eugene Simonides, Warner S. Westenbrink, B. Daan van der Meer, Peter 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms222111906 <jats:p>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.</jats:p> Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes International Journal of Molecular Sciences |
| spellingShingle | Bomer, Nils, Pavez-Giani, Mario G., Deiman, Frederik E., Linders, Annet N., Hoes, Martijn F., Baierl, Christiane L.J., Oberdorf-Maass, Silke U., de Boer, Rudolf A., Silljé, Herman H.W., Berezikov, Eugene, Simonides, Warner S., Westenbrink, B. Daan, van der Meer, Peter, International Journal of Molecular Sciences, Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| title | Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_full | Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_fullStr | Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_full_unstemmed | Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_short | Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| title_sort | selenoprotein dio2 is a regulator of mitochondrial function, morphology and uprmt in human cardiomyocytes |
| title_unstemmed | Selenoprotein DIO2 Is a Regulator of Mitochondrial Function, Morphology and UPRmt in Human Cardiomyocytes |
| topic | Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| url | http://dx.doi.org/10.3390/ijms222111906 |