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Mitochondrial ROS attack DNA readily, generating a variety of DNA damages such as oxidized bases and strand breaks. The major mechanism that cells use to repair oxidized bases such as 8-hydroxyguanine, formamidopyrimidine and 5-hydroxyuracil is base excision repair (BER). [14] BER occurs in both the cell nucleus and in mitochondria.
In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O 2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O 2 H), superoxide (O 2 −), [1] hydroxyl radical (OH.), and singlet oxygen. [2] ROS are pervasive because they are readily produced from O 2, which is ...
As the production of reactive oxygen species by these proton-pumping complexes is greatest at high membrane potentials, it has been proposed that mitochondria regulate their activity to maintain the membrane potential within a narrow range that balances ATP production against oxidant generation. [86]
He found ROS as the main cause of damage to macromolecules, known as "ageing". He later modified his theory because he found that mitochondria were producing and being damaged by ROS, leading him to the conclusion that mitochondria determine ageing. In 1972, he published his theory in the Journal of the American Geriatrics Society. [20]
The theory implicates the mitochondria as the chief target of radical damage, since there is a known chemical mechanism by which mitochondria can produce ROS, mitochondrial components such as mtDNA are not as well protected as nuclear DNA, and by studies comparing damage to nuclear and mtDNA that demonstrate higher levels of radical damage on ...
Illustration of the malate–aspartate shuttle pathway. The malate–aspartate shuttle (sometimes simply the malate shuttle) is a biochemical system for translocating electrons produced during glycolysis across the semipermeable inner membrane of the mitochondrion for oxidative phosphorylation in eukaryotes.
Recent investigations suggest that complex I is a potent source of reactive oxygen species. [53] Complex I can produce superoxide (as well as hydrogen peroxide), through at least two different pathways. During forward electron transfer, only very small amounts of superoxide are produced (probably less than 0.1% of the overall electron flow).
The mitochondrial unfolded protein response (UPR mt) is a cellular stress response related to the mitochondria. The UPR mt results from unfolded or misfolded proteins in mitochondria beyond the capacity of chaperone proteins to handle them. [1] The UPR mt can occur either in the mitochondrial matrix or in the mitochondrial inner membrane. [1]