The role of mitochondrial dehydrogenases in the generation of oxidative stress

Research output: Contribution to journalReview article

42 Citations (Scopus)

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 Ca2+. ROS production by α-GPDH is unique as it does not require Ca2+ 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.

Original languageEnglish
Pages (from-to)757-763
Number of pages7
JournalNeurochemistry international
Volume62
Issue number5
DOIs
Publication statusPublished - Apr 1 2013

Keywords

  • Alpha-glycerophosphate dehydrogenase
  • Alpha-ketoglutarate dehydrogenase
  • Dehydrogenases
  • Mitochondria
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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