Winkler-Stuck K, Kirches E, Mawrin C, Dietzmann K, Lins H, Wallesch C-W, Kunz W S, Wiedemann F R
Klinik für Neurologie, Otto-von-Guericke-Universität, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
J Neural Transm (Vienna). 2005 Apr;112(4):499-518. doi: 10.1007/s00702-004-0195-y. Epub 2004 Aug 3.
The origin and tissue distribution of the mitochondrial dysfunction in Parkinson's disease (PD) remains still a matter of controversy. To re-evaluate a probably free radical-born, generalized mitochondrial impairment in PD, we applied optimized enzymatic assays, high resolution oxygraphic measurements of permeabilized muscle fibers, and application of metabolic control analysis to skeletal muscle samples of 19 PD patients and 36 age-matched controls. We detected decreased activities of respiratory chain complexes I and IV being accompanied by increased flux control coefficients of complexes I and IV on oxygen consumption of muscle fibers. We further investigated if randomly distributed point mutations in two discrete regions of the mitochondrial DNA are increased in PD muscle, and if they could contribute to the mitochondrial impairment. Our data confirm the previously debated presence of a mild mitochondrial defect in skeletal muscle of patients with PD which is accompanied with an about 1.5 to 2-fold increase of point mutated mtDNA.
帕金森病（PD）中线粒体功能障碍的起源和组织分布仍存在争议。为了重新评估PD中可能由自由基产生的全身性线粒体损伤，我们对19例PD患者和36例年龄匹配的对照者的骨骼肌样本应用了优化的酶促测定、对透化肌纤维进行高分辨率氧电极测量以及代谢控制分析。我们检测到呼吸链复合物I和IV的活性降低，同时复合物I和IV对肌纤维氧消耗的流量控制系数增加。我们进一步研究了PD肌肉中线粒体DNA两个离散区域的随机分布点突变是否增加，以及它们是否会导致线粒体损伤。我们的数据证实了之前关于PD患者骨骼肌中存在轻度线粒体缺陷的争论，该缺陷伴随着点突变mtDNA增加约1.5至2倍。
