Laboratory of Biochemistry and Molecular Biology, Department of Pharmaco-Biology, University of Bari, Via E. Orabona 4, 70125 Bari, Italy.
Mitochondrion. 2012 Jan;12(1):156-61. doi: 10.1016/j.mito.2011.07.001. Epub 2011 Jul 18.
Friedreich ataxia (FRDA) is a common form of ataxia caused by decreased expression of the mitochondrial protein frataxin. Oxidative damage of mitochondria is thought to play a key role in the pathogenesis of the disease. Therefore, a possible therapeutic strategy should be directed to an antioxidant protection against mitochondrial damage. Indeed, treatment of FRDA patients with the antioxidant idebenone has been shown to improve neurological functions. The yeast frataxin knock-out model of the disease shows mitochondrial iron accumulation, iron-sulfur cluster defects and high sensitivity to oxidative stress. By flow cytometry analysis we studied reactive oxygen species (ROS) production of yeast frataxin mutant cells treated with two antioxidants, N-acetyl-L-cysteine and a mitochondrially-targeted analog of vitamin E, confirming that mitochondria are the main site of ROS production in this model. Furthermore we found a significant reduction of ROS production and a decrease in the mitochondrial mass in mutant cells treated with rapamycin, an inhibitor of TOR kinases, most likely due to autophagy of damaged mitochondria.
弗里德赖希共济失调（FRDA）是一种常见的共济失调，由线粒体蛋白 frataxin 的表达减少引起。氧化损伤被认为在疾病的发病机制中起关键作用。因此，一种可能的治疗策略应该针对抗氧化剂对线粒体损伤的保护。事实上，用抗氧化剂 idebenone 治疗 FRDA 患者已被证明可以改善神经功能。该疾病的酵母 frataxin 敲除模型显示线粒体铁积累、铁硫簇缺陷和对氧化应激的高度敏感性。通过流式细胞术分析，我们研究了用两种抗氧化剂 N-乙酰-L-半胱氨酸和维生素 E 的线粒体靶向类似物处理酵母 frataxin 突变细胞后活性氧（ROS）的产生，证实线粒体是该模型中 ROS 产生的主要部位。此外，我们发现雷帕霉素（一种 TOR 激酶抑制剂）处理突变细胞后 ROS 产生显著减少，线粒体质量下降，这很可能是由于受损线粒体的自噬。
