Cytoplasmic transfer of platelet mtDNA from elderly patients with Parkinson's disease to mtDNA-less HeLa cells restores complete mitochondrial respiratory function
Cytoplasmic transfer of platelet mtDNA from elderly patients with Parkinson's disease to mtDNA-less HeLa cells restores complete mitochondrial respiratory function
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DOI：
10.1006/bbrc.2000.4113
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发表时间：
2001-01-12
影响因子：
3.1
通讯作者：
Hayashi, JI
中科院分区：
文献类型：
--
作者：
Aomi, Y;Chen, CS;Hayashi, JI
为探讨帕金森病（PD）患者血小板线粒体DNA是否存在导致呼吸酶活性降低的损伤，将老年PD患者和年龄匹配的正常人的血小板线粒体DNA转入无线粒体DNA（rho（0））的HeLa细胞，因为它们的活性受线粒体和核基因组的共同控制。将所得的含有HeLa核基因组作为共同背景的mtDNA再填充的胞质杂交体克隆用于比较呼吸酶活性。无论其mtDNA是从正常人还是从PD患者转移而来，在胞质杂种克隆中均观察到酶活性的显著变化，其中一些表现出平均活性降低20%。因此，导致20%减少的mtDNA突变应该是多态性的，而不是致病性的。另一方面，具有来自线粒体疾病患者的mtDNA突变的致病性对照胞质杂种克隆显示出超出正常变化范围的呼吸酶复合物I活性的显著和特异性下降。这些观察值得重新评估的传统概念，在PD患者的血小板中的复合物I活性是有缺陷的，由于mtDNA突变。(C)北京：科学出版社.
For determination of whether platelet mtDNA in patients with Parkinson's disease (PD) possesses some lesions to reduce respiratory enzyme activities, platelet mtDNA was transferred into mtDNA-less (rho (0)) HeLa cells from aged PD patients and age-matched normal subjects, since their activities were controlled by both mitochondrial and nuclear genomes. The resultant mtDNA-repopulated cybrid clones containing the HeLa nuclear genome as a common background were used for comparison of respiratory enzyme activities. Remarkable variations of the enzyme activities were observed in the cybrid clones, irrespective of whether their mtDNA was transferred from normal subjects or PD patients, and some of them showed 20% reduction of average activities. Thus, the mtDNA mutations responsible for inducing 20% reduction should be polymorphic rather than pathogenic. On the other hand, pathogenic control cybrid clones possessing mtDNA mutations from patients with mitochondrial disorders showed significant and specific decline of respiratory enzyme complex I activity beyond the normal range of the variations. These observations warrant reassessment of the conventional concept that complex I activity in platelets of PD patients is defective due to mtDNA mutations. (C) 2001 Academic Press.