Mitochondrial Production of Hydrogen Peroxide Regulation by Nitric Oxide and the Role of Ubisemiquinone

Abstract

SummaryMitochondria are considered the major cellular site for hydrogen peroxide production, a process that is kinetically controlled by the availability of oxygen and nitric oxide to cytochrome oxidase and of ADP to

Oxidative stress, chronic disease, and muscle wasting

“…Superoxide is generated at both complex I and III of the electron transport chain,119 but may also be produced by complex II, especially when damaged by oxidative stress or aging 287. Superoxide generated by mitochondria represents approximately 1% of total oxygen consumption 21. However, net release of superoxide by mitochondria is much lower due to conversion to H 2 O 2 by manganese superoxide dismutase (MnSOD) in the mitochondrial matrix and by copper–zinc SOD (CuZnSOD) in the intermembrane space.…”

“…However, net release of superoxide by mitochondria is much lower due to conversion to H 2 O 2 by manganese superoxide dismutase (MnSOD) in the mitochondrial matrix and by copper–zinc SOD (CuZnSOD) in the intermembrane space. The resulting H 2 O 2 freely diffuses to the cytoplasm and constitutes 20%–30% of the steady‐state level 21, 119. In tissues with a higher aerobic rate, such as skeletal muscle and heart, the contribution can be as much as 96% 21, 116.…”

“…The resulting H 2 O 2 freely diffuses to the cytoplasm and constitutes 20%–30% of the steady‐state level 21, 119. In tissues with a higher aerobic rate, such as skeletal muscle and heart, the contribution can be as much as 96% 21, 116. This level is estimated to be 10–100 nM in hepatocytes or as much as 1 μM in breast cancer and melanoma cells 21.…”

“…In tissues with a higher aerobic rate, such as skeletal muscle and heart, the contribution can be as much as 96% 21, 116. This level is estimated to be 10–100 nM in hepatocytes or as much as 1 μM in breast cancer and melanoma cells 21. Hydrogen peroxide conversion to damaging radicals such as OH· is catalyzed by non‐enzymatic transition‐metal reactions, most notably by Fe 2+ (Fenton reaction96).…”

Why females live longer than males? Importance of the upregulation of longevity‐associated genes by oestrogenic compounds

“…We searched for an explanation of the remarkable difference in free radical production between genders. Since the mitochondrial steady‐state concentrations of and H 2 O 2 are defined by the ratio of the rates of production and utilization of these species, we determined the mitochondrial activity and expression of Mn‐SOD and GPx [19]. Table 1 shows that the expression of Mn‐SOD, i.e., the mitochondrial SOD isoenzyme, is approximately double in females than in males.…”