Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Int J Mol Sci. 2018 May 26;19(6):1582. doi: 10.3390/ijms19061582.
We examine the effect of oxidative stress on the stability of mitochondrial respiratory complexes and their association into supercomplexes (SCs) in the neuron-specific Rieske iron sulfur protein (RISP) and COX10 knockout (KO) mice. Previously we reported that these two models display different grades of oxidative stress in distinct brain regions. Using blue native gel electrophoresis, we observed a redistribution of the architecture of SCs in KO mice. Brain regions with moderate levels of oxidative stress (cingulate cortex of both COX10 and RISP KO and hippocampus of the RISP KO) showed a significant increase in the levels of high molecular weight (HMW) SCs. High levels of oxidative stress in the piriform cortex of the RISP KO negatively impacted the stability of CI, CIII and SCs. Treatment of the RISP KO with the mitochondrial targeted antioxidant mitoTEMPO preserved the stability of respiratory complexes and formation of SCs in the piriform cortex and increased the levels of glutathione peroxidase. These results suggest that mild to moderate levels of oxidative stress can modulate SCs into a more favorable architecture of HMW SCs to cope with rising levels of free radicals and cover the energetic needs.
我们研究了氧化应激对线粒体呼吸复合物稳定性及其在神经元特异性 Rieske 铁硫蛋白（RISP）和细胞色素 c 氧化酶 10 缺失（KO）小鼠中超复合物（SCs）形成的影响。之前我们报道过，这两种模型在不同的脑区显示出不同程度的氧化应激。通过蓝色 native 凝胶电泳，我们观察到 KO 小鼠中 SCs 结构的重新分布。氧化应激程度适中的脑区（两种 COX10 和 RISP KO 的扣带皮层和 RISP KO 的海马体）中高分子量（HMW）SC 的水平显著增加。RISP KO 梨状皮层的高水平氧化应激对 CI、CIII 和 SCs 的稳定性产生负面影响。用线粒体靶向抗氧化剂 mitoTEMPO 处理 RISP KO，可维持梨状皮层呼吸复合物的稳定性和 SCs 的形成，并增加谷胱甘肽过氧化物酶的水平。这些结果表明，轻度至中度氧化应激水平可以将 SCs 调节为更有利的 HMW SC 结构，以应对自由基水平的升高，并满足能量需求。
