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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Mathematical biosciences Cancer systems biology Cancer Science Q
Acceso en línea:	https://doaj.org/article/f4f90a877f724fafa3cbfea6ae94db1b
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spelling	oai:doaj.org-article:f4f90a877f724fafa3cbfea6ae94db1b2021-11-20T05:10:44ZMetabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown2589-004210.1016/j.isci.2021.103366https://doaj.org/article/f4f90a877f724fafa3cbfea6ae94db1b2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013377https://doaj.org/toc/2589-0042Summary: 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.Adam KrysztofiakKlaudia SzymonowiczJulian HlouschekKexu XiangChristoph WaterkampSafa LarafaIsabell GoettingSilvia Vega-Rubin-de-CelisCarsten TheissVeronika MatschkeDaniel HoffmannVerena JendrossekJohann MatschkeElsevierarticleMathematical biosciencesCancer systems biologyCancerScienceQENiScience, Vol 24, Iss 11, Pp 103366- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mathematical biosciences Cancer systems biology Cancer Science Q
spellingShingle	Mathematical biosciences Cancer systems biology Cancer Science Q 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
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.
format	article
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
title	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_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_sort	metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f4f90a877f724fafa3cbfea6ae94db1b
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Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown

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