Assembly defects induce oxidative stress in inherited mitochondrial complex I deficiency

摘要: Complex I (CI) deficiency is the most common respiratory chain defect representing more than 30% of mitochondrial diseases. CI an L-shaped multi-subunit complex with a peripheral arm protruding into matrix and membrane arm. sequentially assembled main assembly intermediates: P (pumping), Q (Quinone) N (NADH dehydrogenase) modules. In this study, we analyzed 11 fibroblast cell lines derived from patients inherited resulting mutations in nuclear or DNA impacting these different patient cells carrying mutation located CI, blue native-polyacrylamide gel electrophoresis (BN-PAGE) revealed significant reduction fully enzyme accumulation intermediates module. defect, NADH dehydrogenase activity was partly functional, even though not assembled. We further demonstrated that functional module responsible for ROS production through reduced flavin mononucleotide. Due to FMN site re-oxidized leading oxidative stress defect. These findings only highlight relationship between stress, but also show suitability BN-PAGE analysis evaluating consequences dysfunction. Moreover, data suggest use antioxidants may be particularly relevant displaying