Mitochondrial H<sub>2</sub>O<sub>2</sub> release does not directly cause damage to chromosomal DNA.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38548751.
- Also identified by DOI 10.1038/s41467-024-47008-x and PMC identifier 10978998.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub>. Nuclear H<sub>2</sub>O<sub>2</sub> gives rise to DNA damage and mutations and a subsequent p53 dependent cell cycle arrest. Mitochondrial H<sub>2</sub>O<sub>2</sub> release shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. We conclude that H<sub>2</sub>O<sub>2</sub> released from mitochondria is unlikely to directly damage nuclear genomic DNA, limiting its contribution to oncogenic transformation and aging.
Medical subject headings
- Hydrogen Peroxide
- Mitochondria