Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown
Summary: Cancer bioenergetics fuel processes necessary to maintain viability and growth under stress conditions. We hypothesized that cancer metabolism supports the repair of radiation-induced DNA double-stranded breaks (DSBs). We combined the systematic collection of metabolic and radiobiological d...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221013377 |
| _version_ | 1798034955164450816 |
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| author | Adam Krysztofiak Klaudia Szymonowicz Julian Hlouschek Kexu Xiang Christoph Waterkamp Safa Larafa Isabell Goetting Silvia Vega-Rubin-de-Celis Carsten Theiss Veronika Matschke Daniel Hoffmann Verena Jendrossek Johann Matschke |
| author_facet | Adam Krysztofiak Klaudia Szymonowicz Julian Hlouschek Kexu Xiang Christoph Waterkamp Safa Larafa Isabell Goetting Silvia Vega-Rubin-de-Celis Carsten Theiss Veronika Matschke Daniel Hoffmann Verena Jendrossek Johann Matschke |
| author_sort | Adam Krysztofiak |
| collection | DOAJ |
| description | Summary: Cancer bioenergetics fuel processes necessary to maintain viability and growth under stress conditions. We hypothesized that cancer metabolism supports the repair of radiation-induced DNA double-stranded breaks (DSBs). We combined the systematic collection of metabolic and radiobiological data from a panel of irradiated cancer cell lines with mathematical modeling and identified a common metabolic response with impact on the DSB repair kinetics, including a mitochondrial shutdown followed by compensatory glycolysis and resumption of mitochondrial function. Combining ionizing radiation (IR) with inhibitors of the compensatory glycolysis or mitochondrial respiratory chain slowed mitochondrial recovery and DNA repair kinetics, offering an opportunity for therapeutic intervention. Mathematical modeling allowed us to generate new hypotheses on general and individual mechanisms of the radiation response with relevance to DNA repair and on metabolic vulnerabilities induced by cancer radiotherapy. These discoveries will guide future mechanistic studies for the discovery of metabolic targets for overcoming intrinsic or therapy-induced radioresistance. |
| first_indexed | 2024-04-11T20:50:34Z |
| format | Article |
| id | doaj.art-f4f90a877f724fafa3cbfea6ae94db1b |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-11T20:50:34Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-f4f90a877f724fafa3cbfea6ae94db1b2022-12-22T04:03:51ZengElsevieriScience2589-00422021-11-012411103366Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdownAdam Krysztofiak0Klaudia Szymonowicz1Julian Hlouschek2Kexu Xiang3Christoph Waterkamp4Safa Larafa5Isabell Goetting6Silvia Vega-Rubin-de-Celis7Carsten Theiss8Veronika Matschke9Daniel Hoffmann10Verena Jendrossek11Johann Matschke12Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyBioinformatics and Computational Biophysics, University of Duisburg-Essen, 45117 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyDepartment of Cytology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, 44801 Bochum, GermanyDepartment of Cytology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, 44801 Bochum, GermanyBioinformatics and Computational Biophysics, University of Duisburg-Essen, 45117 Essen, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany; Corresponding authorInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany; Corresponding authorSummary: Cancer bioenergetics fuel processes necessary to maintain viability and growth under stress conditions. We hypothesized that cancer metabolism supports the repair of radiation-induced DNA double-stranded breaks (DSBs). We combined the systematic collection of metabolic and radiobiological data from a panel of irradiated cancer cell lines with mathematical modeling and identified a common metabolic response with impact on the DSB repair kinetics, including a mitochondrial shutdown followed by compensatory glycolysis and resumption of mitochondrial function. Combining ionizing radiation (IR) with inhibitors of the compensatory glycolysis or mitochondrial respiratory chain slowed mitochondrial recovery and DNA repair kinetics, offering an opportunity for therapeutic intervention. Mathematical modeling allowed us to generate new hypotheses on general and individual mechanisms of the radiation response with relevance to DNA repair and on metabolic vulnerabilities induced by cancer radiotherapy. These discoveries will guide future mechanistic studies for the discovery of metabolic targets for overcoming intrinsic or therapy-induced radioresistance.http://www.sciencedirect.com/science/article/pii/S2589004221013377Mathematical biosciencesCancer systems biologyCancer |
| spellingShingle | Adam Krysztofiak Klaudia Szymonowicz Julian Hlouschek Kexu Xiang Christoph Waterkamp Safa Larafa Isabell Goetting Silvia Vega-Rubin-de-Celis Carsten Theiss Veronika Matschke Daniel Hoffmann Verena Jendrossek Johann Matschke Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown iScience Mathematical biosciences Cancer systems biology Cancer |
| title | Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown |
| title_full | Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown |
| title_fullStr | Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown |
| title_full_unstemmed | Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown |
| title_short | Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown |
| title_sort | metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown |
| topic | Mathematical biosciences Cancer systems biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221013377 |
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