Peptide Oxidation leads to N/A, Mitochondrial dysfunction 1

The mitochondrion consist of a plethora of antioxidant enzymes to defend against oxidative stress, such as catalases, which has been found in the liver, glutathione peroxidase, and thioredoxin peroxidase ^{[1] [2]}. At the same time, the mitochondrion itself is one of the main sources of intracellular ROS formation ^[3].

NAD(P)H plays a central role in the redox state of the mitochondrion: NADP is reduced, in part, by the activity of the NADH/NADP transhydrogenase that functions as a proton pump ^[1] and has a reductive effect on glutathione and thioredoxin. This directly links mitochondrial coupling and the membrane potential to the redox potential. As a consequence, an imbalance in the NAD(P) redox status can lead to mitochondrial permeability transition (MPT), a nonselective permeabilization of the inner mitochondrial membrane ^[4]. An imbalance of the redox state of these pyridine nucleotides and thus condition of oxidative stress can lead to an increased influx of Ca2+, which in turn facilitates activation of the mitochondrial permeability transition pore, leading to apoptosis ^{[5] [6]}.

Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

Quantitative understanding of this KER is low. Inhibition of the ROS source could delay mitochondrial damage, and treatment with an antioxidant could partly inhibit the effect on the mitochondrion.

^[10]: rat

^[7]: rat

^[8]: rat

^[9]: mouse