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| Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDPm) is induced by reactive oxygen species (ROS) and decreases in the expression of IDPm elevate ROS generation, DNA fragmentation, lipid peroxidation, and simultaneous mitochondrial damage with a considerable reduction in ATP. Cell damage by oxidative stress and ROS has been factors in human conditions such as aging, alcohol mediated organ damage, neurodegenerative disease, types of cancers, cardiovascular diseases and UV-mediated skin disorders. The overproduction of IDPm proteins protects the cells from ROS-induced damage. Mitochondria are highly susceptible to ROS damage by effecting mitochondrial enzymes directly or by causing mutations in the DNA. ROS may also cause apoptosis in mitochondria. Tissues vary in their expression of IDPm, many oxygen-consuming tissues show high amounts of IDPm, while tissues vulnerable to oxidative injury showed low levels of IDPm. Jo, S.H., et al. determined intracellular ROS production and associated cell death rate are inversely related to levels of transduced IDPm protein. This supported the protective role of IDPm against ROS-induced cell death. IDPm works as a key enzyme in defense against oxidative damage by supplying NADPH in the mitochondria. The NADPH aids in the regeneration of GSH or thioredoxin in mitochondria. This study also determined the 5’-promoter region of the IDPm gene may contain the “antioxidative responsive element” sequence that also responds to exogenous stressors (7). |
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