Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression
Tafazzin—an acyltransferase—is involved in cardiolipin (CL) remodeling. CL is associated with mitochondrial function, structure and more recently with cell proliferation. Various tafazzin isoforms exist in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study was...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.931017/full |
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| author | Gayatri Jagirdar Matthias Elsner Christian Scharf Stefan Simm Katrin Borucki Daniela Peter Michael Lalk Karen Methling Michael Linnebacher Mathias Krohn Carmen Wolke Uwe Lendeckel |
| author_facet | Gayatri Jagirdar Matthias Elsner Christian Scharf Stefan Simm Katrin Borucki Daniela Peter Michael Lalk Karen Methling Michael Linnebacher Mathias Krohn Carmen Wolke Uwe Lendeckel |
| author_sort | Gayatri Jagirdar |
| collection | DOAJ |
| description | Tafazzin—an acyltransferase—is involved in cardiolipin (CL) remodeling. CL is associated with mitochondrial function, structure and more recently with cell proliferation. Various tafazzin isoforms exist in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study was to investigate if specific isoforms like Δ5 can restore the wild type phenotype with respect to CL composition, cellular proliferation and gene expression profile. In addition, we aimed to determine the molecular mechanism by which tafazzin can modulate gene expression by applying promoter analysis and (Ingenuity Pathway Analyis) IPA to genes regulated by TAZ-deficiency. Expression of Δ5 and rat full length TAZ in C6-TAZ- cells could fully restore CL composition and—as proven for Δ5—this is naturally associated with restoration of mitochondrial respiration. A similar restoration of CL-composition could not be observed after re-expression of an enzymatically dead full-length rat TAZ (H69L; TAZMut). Re-expression of only rat full length TAZ could restore proliferation rate. Surprisingly, the Δ5 variant failed to restore wild-type proliferation. Further, as expected, re-expression of the TAZMut variant completely failed to reverse the gene expression changes, whereas re-expression of the TAZ-FL variant largely did so and the Δ5 variant to somewhat less extent. Very likely TAZ-deficiency provokes substantial long-lasting changes in cellular lipid metabolism which contribute to changes in proliferation and gene expression, and are not or only very slowly reversible. |
| first_indexed | 2024-04-11T21:15:14Z |
| format | Article |
| id | doaj.art-ccfbeaf0a01a4f44a636a95043149365 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T21:15:14Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-ccfbeaf0a01a4f44a636a950431493652022-12-22T04:02:51ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-07-011310.3389/fgene.2022.931017931017Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene ExpressionGayatri Jagirdar0Matthias Elsner1Christian Scharf2Stefan Simm3Katrin Borucki4Daniela Peter5Michael Lalk6Karen Methling7Michael Linnebacher8Mathias Krohn9Carmen Wolke10Uwe Lendeckel11Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, Greifswald, GermanyInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, GermanyDepartment of Otorhinolaryngology, Head, and Neck Surgery, University Medicine Greifswald, Greifswald, GermanyInstitute of Bioinformatics, University Medicine Greifswald, Greifswald, GermanyInstitute of Clinical Chemistry, Department of Pathobiochemistry, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, GermanyInstitute of Clinical Chemistry, Department of Pathobiochemistry, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, GermanyInstitute of Biochemistry, University of Greifswald, Greifswald, GermanyInstitute of Biochemistry, University of Greifswald, Greifswald, GermanyDepartment of General Surgery, Molecular Oncology, and Immunotherapy, Rostock University Medical Center, Rostock, GermanyDepartment of General Surgery, Molecular Oncology, and Immunotherapy, Rostock University Medical Center, Rostock, GermanyInstitute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, Greifswald, GermanyInstitute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, Greifswald, GermanyTafazzin—an acyltransferase—is involved in cardiolipin (CL) remodeling. CL is associated with mitochondrial function, structure and more recently with cell proliferation. Various tafazzin isoforms exist in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study was to investigate if specific isoforms like Δ5 can restore the wild type phenotype with respect to CL composition, cellular proliferation and gene expression profile. In addition, we aimed to determine the molecular mechanism by which tafazzin can modulate gene expression by applying promoter analysis and (Ingenuity Pathway Analyis) IPA to genes regulated by TAZ-deficiency. Expression of Δ5 and rat full length TAZ in C6-TAZ- cells could fully restore CL composition and—as proven for Δ5—this is naturally associated with restoration of mitochondrial respiration. A similar restoration of CL-composition could not be observed after re-expression of an enzymatically dead full-length rat TAZ (H69L; TAZMut). Re-expression of only rat full length TAZ could restore proliferation rate. Surprisingly, the Δ5 variant failed to restore wild-type proliferation. Further, as expected, re-expression of the TAZMut variant completely failed to reverse the gene expression changes, whereas re-expression of the TAZ-FL variant largely did so and the Δ5 variant to somewhat less extent. Very likely TAZ-deficiency provokes substantial long-lasting changes in cellular lipid metabolism which contribute to changes in proliferation and gene expression, and are not or only very slowly reversible.https://www.frontiersin.org/articles/10.3389/fgene.2022.931017/fullBarth syndromecardiolipincellular proliferationgene expressiontafazzinBarth syndrome (BTHS) |
| spellingShingle | Gayatri Jagirdar Matthias Elsner Christian Scharf Stefan Simm Katrin Borucki Daniela Peter Michael Lalk Karen Methling Michael Linnebacher Mathias Krohn Carmen Wolke Uwe Lendeckel Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression Frontiers in Genetics Barth syndrome cardiolipin cellular proliferation gene expression tafazzin Barth syndrome (BTHS) |
| title | Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression |
| title_full | Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression |
| title_fullStr | Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression |
| title_full_unstemmed | Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression |
| title_short | Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression |
| title_sort | re expression of tafazzin isoforms in taz deficient c6 glioma cells restores cardiolipin composition but not proliferation rate and alterations in gene expression |
| topic | Barth syndrome cardiolipin cellular proliferation gene expression tafazzin Barth syndrome (BTHS) |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.931017/full |
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