Mitochondrial Respiratory Dysfunction in Familiar Parkinsonism Associated with PINK1 Mutation
Mitochondrial Respiratory Dysfunction in Familiar Parkinsonism Associated with PINK1 Mutation
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DOI：
10.1007/s11064-008-9729-2
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发表时间：
2008-12-01
影响因子：
4.4
通讯作者：
Papa, Sergio
中科院分区：
文献类型：
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作者：
Piccoli, Claudia;Sardanelli, Annamaria;Papa, Sergio
在本研究中，对一例携带PINK1基因W437X纯合无义突变的早发性帕金森患者成纤维细胞的线粒体呼吸功能进行了全面研究。与正常成纤维细胞相比，患者成纤维细胞线粒体的呼吸活性降低，呼吸控制率降低，细胞内的ATP供应主要依赖于糖酵解产物的增加。氧化磷酸化复合体的数量、比活性和亚基类型均正常。然而，观察到细胞色素c含量显著下降，这与细胞色素c氧化酶原位活性降低有关。患者成纤维细胞线粒体中ROS的测量显示，通过抑制复合体I，增强了O-2(中心点-)和过氧化氢的产生，然而，没有观察到谷胱甘肽为基础的氧化还原缓冲的变化。
In the present study mitochondrial respiratory function of fibroblasts from a patient affected by early-onset Parkinsonism carrying the homozygous W437X nonsense mutation in the PINK1 gene has been thoroughly characterized. When compared with normal fibroblasts, the patient's fibroblast mitochondria exhibited a lower respiratory activity and a decreased respiratory control ratio with cellular ATP supply relying mainly on enhanced glycolytic production. The quantity, specific activity and subunit pattern of the oxidative phosphorylation complexes were normal. However, a significant decrease of the cellular cytochrome c content was observed and this correlated with a reduced cytochrome c oxidase in situ-activity. Measurement of ROS revealed in mitochondria of the patient's fibroblasts enhanced O-2(center dot-) and H2O2 production abrogated by inhibition of complex I. No change in the glutathione-based redox buffering was, however, observed.