The role of mitochondrial dehydrogenases in the generation of oxidative stress
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Updated: May 14, 2026

Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
Vera Adam-Vizi1, Laszlo Tretter
1Department of Medical Biochemistry, Semmelweis University, Laboratory of Neurobiochemistry, Hungarian Academy of Sciences, Budapest, Hungary. adam.veronika@med.semmelweis-univ.hu
Abstract:
In addition to complexes in the respiratory chain, few dehydrogenases playing key roles in the physiological metabolism in neurons, are able to generate reactive oxygen species (ROS) in mitochondria. One of them is the Krebs cycle enzyme, α-ketoglutarate dehydrogenase (α-KGDH), which is capable of producing superoxide and hydrogen peroxide by the E3 subunit of the enzyme regulated by changes in the NADH/NAD(+) ratio. Mutations in the E3 subunit known to be related to diseases in humans were shown to have increased ROS-forming ability. α-Glycerophosphate dehydrogenase (α-GPDH) located on the outer surface of the inner membrane can also generate ROS, which is stimulated by Ca(2+). ROS production by α-GPDH is unique as it does not require Ca(2+) uptake and it is observed in respiring as well as damaged, bioenergetically incompetent mitochondria. The possible role of ROS generation by these dehydrogenases in brain pathology is discussed in this review.
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