Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA
Abstract Reactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of chromosomal DNA mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondria can directly damage nuclear DNA...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47008-x |
| _version_ | 1797233482734239744 |
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| author | Daan M. K. van Soest Paulien E. Polderman Wytze T. F. den Toom Janneke P. Keijer Markus J. van Roosmalen Tim M. F. Leyten Johannes Lehmann Susan Zwakenberg Sasha De Henau Ruben van Boxtel Boudewijn M. T. Burgering Tobias B. Dansen |
| author_facet | Daan M. K. van Soest Paulien E. Polderman Wytze T. F. den Toom Janneke P. Keijer Markus J. van Roosmalen Tim M. F. Leyten Johannes Lehmann Susan Zwakenberg Sasha De Henau Ruben van Boxtel Boudewijn M. T. Burgering Tobias B. Dansen |
| author_sort | Daan M. K. van Soest |
| collection | DOAJ |
| description | Abstract Reactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of chromosomal DNA mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondria can directly damage nuclear DNA is largely lacking. In this study, we investigated the effects of H2O2 released by mitochondria or produced at the nucleosomes using a titratable chemogenetic approach. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2. Nuclear H2O2 gives rise to DNA damage and mutations and a subsequent p53 dependent cell cycle arrest. Mitochondrial H2O2 release shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. We conclude that H2O2 released from mitochondria is unlikely to directly damage nuclear genomic DNA, limiting its contribution to oncogenic transformation and aging. |
| first_indexed | 2024-04-24T16:16:53Z |
| format | Article |
| id | doaj.art-b371c4d981744db88fc299f04a79fc07 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T16:16:53Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b371c4d981744db88fc299f04a79fc072024-03-31T11:25:58ZengNature PortfolioNature Communications2041-17232024-03-0115111610.1038/s41467-024-47008-xMitochondrial H2O2 release does not directly cause damage to chromosomal DNADaan M. K. van Soest0Paulien E. Polderman1Wytze T. F. den Toom2Janneke P. Keijer3Markus J. van Roosmalen4Tim M. F. Leyten5Johannes Lehmann6Susan Zwakenberg7Sasha De Henau8Ruben van Boxtel9Boudewijn M. T. Burgering10Tobias B. Dansen11Center for Molecular Medicine, University Medical Center UtrechtCenter for Molecular Medicine, University Medical Center UtrechtCenter for Molecular Medicine, University Medical Center UtrechtCenter for Molecular Medicine, University Medical Center UtrechtPrincess Máxima Center for Pediatric OncologyCenter for Molecular Medicine, University Medical Center UtrechtCenter for Molecular Medicine, University Medical Center UtrechtCenter for Molecular Medicine, University Medical Center UtrechtCenter for Molecular Medicine, University Medical Center UtrechtPrincess Máxima Center for Pediatric OncologyCenter for Molecular Medicine, University Medical Center UtrechtCenter for Molecular Medicine, University Medical Center UtrechtAbstract Reactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of chromosomal DNA mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondria can directly damage nuclear DNA is largely lacking. In this study, we investigated the effects of H2O2 released by mitochondria or produced at the nucleosomes using a titratable chemogenetic approach. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2. Nuclear H2O2 gives rise to DNA damage and mutations and a subsequent p53 dependent cell cycle arrest. Mitochondrial H2O2 release shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. We conclude that H2O2 released from mitochondria is unlikely to directly damage nuclear genomic DNA, limiting its contribution to oncogenic transformation and aging.https://doi.org/10.1038/s41467-024-47008-x |
| spellingShingle | Daan M. K. van Soest Paulien E. Polderman Wytze T. F. den Toom Janneke P. Keijer Markus J. van Roosmalen Tim M. F. Leyten Johannes Lehmann Susan Zwakenberg Sasha De Henau Ruben van Boxtel Boudewijn M. T. Burgering Tobias B. Dansen Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA Nature Communications |
| title | Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA |
| title_full | Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA |
| title_fullStr | Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA |
| title_full_unstemmed | Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA |
| title_short | Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA |
| title_sort | mitochondrial h2o2 release does not directly cause damage to chromosomal dna |
| url | https://doi.org/10.1038/s41467-024-47008-x |
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