Mitochondrial proteomics reveal potential targets involved in mitochondrial abnormalities of desminopathy
Mitochondrial proteomics reveal potential targets involved in mitochondrial abnormalities of desminopathy
复制标题
线粒体蛋白质组学揭示了与结膜病线粒体异常相关的潜在靶标
DOI：
10.5414/np300969
复制
发表时间：
2017-01-01
影响因子：
1.1
通讯作者：
Hong, Daojun
中科院分区：
文献类型：
--
作者：
Chen, Yunqing;Zheng, Junjun;Hong, Daojun
目的：探讨结蛋白缺陷导致结蛋白病线粒体异常的机制。材料和方法：原代成肌细胞分离肌活检结蛋白病患者线粒体异常。从成肌细胞分离的线粒体中进行线粒体蛋白质的二维凝胶电泳分析。进行免疫染色、免疫印迹和线粒体功能测试以确认蛋白质组学结果。结果：在线粒体蛋白质组学中发现42个蛋白质存在显著差异。功能聚类分析确定了几个与线粒体通透性转换孔（MPTP）复合物的调节相关的蛋白质。强免疫反应性、MPTP开放增加和氧化应激水平升高也证实了蛋白表达的模式。结论：这项研究提供了一个整体的观点，线粒体蛋白质组可塑性的情况下，desminopathy与线粒体异常。MPTP相关蛋白的表达模式表明结蛋白可能影响MPTP复合物，作为参与结蛋白病中线粒体功能障碍的潜在靶点。然而，确切的基本机制仍有待阐明。
Aims: To investigate the underlying mechanisms of how the defects of desmin cause mitochondrial abnormalities in desminopathy. Material and methods: Primary myoblasts were isolated from muscle biopsy of a desminopathy patient with mitochondrial abnormalities. Two-dimensional gel electrophoresis analyses of mitochondrial proteins were performed in mitochondria isolated from myoblasts. Immunostaining, immunoblot, and mitochondrial function tests were carried out to confirm the proteomic results. Results: 42 proteins were found with significant expression differences in the mitochondrial proteomics. Several proteins associated with regulation of the mitochondrial permeability transition pore (MPTP) complex were identified in functional cluster analysis. The patterns of protein expression were also confirmed by strong immunoreactivity, increased MPTP opening and elevated level of oxidative stress. Conclusions: The study provides an overall perspective of the mitochondrial proteome plasticity in a case of desminopathy with mitochondrial abnormalities. The expression patterns of protein associated with MPTP indicate that desmin might affect MPTP complex as potential targets involved in mitochondrial dysfunction in desminopathy. However, the precise underlying mechanism remains to be elucidated.