Ataxia telangiectasia mutated influences cytochrome c oxidase activity

作者：Patel Akshar Y; McDonald Todd M; Spears Larry D; Ching James Kain; Fisher Jonathan S^*

来源：Biochemical and Biophysical Research Communications, 2011, 405(4): 599-603.

DOI：10.1016/j.bbrc.2011.01.075

• Ataxia telangiectasia mutated
• Cytochrome c oxidase
• Mitochondria
• Glucose 6-phosphate dehydrogenase
• KU-55933

Cells lacking ataxia telangiectasia mutated (ATM) have impaired mitochondrial function. Furthermore, mammalian cells lacking ATM have increased levels of reactive oxygen species (ROS) as well as mitochondrial DNA (mtDNA) deletions in the region encoding for cytochrome c oxidase (COX). We hypothesized that ATM specifically influences COX activity in skeletal muscle. COX activity was similar to 40% lower in tibialis anterior from ATM-deficient mice than for wild-type mice (P < 0.01, n = 9/group). However, there were no ATM-related differences in activity of succinate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, or complex III. Incubation of wild-type extensor digitorum longus muscles for 1 h with the ATM inhibitor KU55933 caused a similar to 50% reduction (P < 0.05, n = 5/group) in COX activity compared to muscles incubated with vehicle alone. Among the control muscles and muscles treated with the ATM inhibitor, COX activity was correlated (r = 0.61, P < 0.05) with activity of glucose 6-phosphate dehydrogenase, a key determinant of antioxidant defense through production of NADPH. Overall, the findings suggest that ATM has a protective role for COX activity.

• 出版日期2011-2-25