The role of mitochondrial dehydrogenases in the generation of oxidative stress

被引:63
作者
Adam-Vizi, Vera [1 ]
Tretter, Laszlo [1 ]
机构
[1] Semmelweis Univ, Dept Med Biochem, Hungarian Acad Sci, Lab Neurobiochem, H-1094 Budapest, Hungary
关键词
Mitochondria; Reactive oxygen species; Dehydrogenases; Oxidative stress; Alpha-ketoglutarate dehydrogenase; Alpha-glycerophosphate dehydrogenase; ALPHA-KETOGLUTARATE DEHYDROGENASE; GLYCEROL-PHOSPHATE DEHYDROGENASE; HYDROGEN-PEROXIDE PRODUCTION; OXYGEN SPECIES GENERATION; ADIPOSE-TISSUE MITOCHONDRIA; DEPENDENT ENZYME CHANGES; BRAIN MITOCHONDRIA; H2O2; GENERATION; GLYCEROL-3-PHOSPHATE DEHYDROGENASE; GLYCEROPHOSPHATE DEHYDROGENASE;
D O I
10.1016/j.neuint.2013.01.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, alpha-ketoglutarate dehydrogenase (alpha-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. alpha-Glycerophosphate dehydrogenase (alpha-GPDH) located on the outer surface of the inner membrane can also generate ROS, which is stimulated by Ca2+. ROS production by alpha-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. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:757 / 763
页数:7
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