Fibroblast mitochondria in idiopathic Parkinson's disease display morphological changes and enhanced resistance to depolarization
Fibroblast mitochondria in idiopathic Parkinson's disease display morphological changes and enhanced resistance to depolarization
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DOI：
10.1038/s41598-020-58505-6
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发表时间：
2020-01-31
影响因子：
4.6
通讯作者：
Diederich, N. J.
中科院分区：
文献类型：
--
作者：
Antony, P. M. A.;Kondratyeva, O.;Diederich, N. J.
线粒体功能障碍是特发性帕金森病 (IPD) 的一个标志。在这里，我们建立了来自 IPD 患者的原代成纤维细胞中线粒体形态和功能的可筛选表型。对 41 名中期 IPD 患者和 21 名年龄匹配的健康对照者进行了上臂打孔皮肤活检。在单细胞水平上，IPD 患者的基础线粒体膜电位 (.m) 高于对照组。同样，在羰基氰化物 4-(三氟甲氧基)苯腙 (FCCP) 应激下，IPD 患者的剩余 Psi m 增加。对线粒体形态参数的分析显示，IPD 患者的线粒体连接性显着降低，14 个线粒体形态参数中有 9 个与对照组不同。显着的线粒体形态变化包括节点程度、平均体积、骨架大小、周长、形状因子、节点计数、侵蚀体计数、端点和线粒体计数（所有 P 值 < 0.05）。这些功能数据表明，IPD 患者接受质子载体 FCCP 治疗后，去极化抵抗力增加，而形态测量数据显示，线粒体连接性降低，线粒体碎片增加。
Mitochondrial dysfunction is a hallmark in idiopathic Parkinson's disease (IPD). Here, we established screenable phenotypes of mitochondrial morphology and function in primary fibroblasts derived from patients with IPD. Upper arm punch skin biopsy was performed in 41 patients with mid-stage IPD and 21 age-matched healthy controls. At the single-cell level, the basal mitochondrial membrane potential (.m) was higher in patients with IPD than in controls. Similarly, under carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) stress, the remaining Psi m was increased in patients with IPD. Analysis of mitochondrial morphometric parameters revealed significantly decreased mitochondrial connectivity in patients with IPD, with 9 of 14 morphometric mitochondrial parameters differing from those in controls. Significant morphometric mitochondrial changes included the node degree, mean volume, skeleton size, perimeter, form factor, node count, erosion body count, endpoints, and mitochondria count (all P-values < 0.05). These functional data reveal that resistance to depolarization was increased by treatment with the protonophore FCCP in patients with IPD, whereas morphometric data revealed decreased mitochondrial connectivity and increased mitochondrial fragmentation.