Researchers here report on an interesting in vitro demonstration, in which they show that hydrogen peroxide (H2O2) generated in mitochondria does not cause nuclear DNA damage. Oxidizing molecules generated as a byproduct of mitochondrial generation of the chemical energy store molecule adenosine triphosphate (ATP) are thought to be important in aging. Oxidative stress is a feature of aging and age-related changes to mitochondrial structure, dynamics, and function. Oxidative damage to nuclear DNA is also a feature of this cell-wide oxidative stress, and it is commonly thought that mitochondria are the source of this stress and thus this damage. But perhaps they are not.
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.
Link: https://doi.org/10.1...467-024-47008-x
View the full article at FightAging
