Fused in sarcoma (FUS) is a DNA/RNA‐binding protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. The exact molecular mechanisms by which FUS results in neurotoxicity have not yet been fully elucidated. Here, we found that parkin is a genetic suppressor of defective phenotypes induced by exogenous human wild type FUS in Drosophila. Although parkin overexpression did not modulate the FUS protein expression level, the locomotive defects in FUS‐expressing larvae and adult flies were rescued by parkin expression. We found that FUS expression in muscle tissues resulted in a reduction of the levels and assembly of mitochondrial complex I and III subunits, as well as decreased ATP. Remarkably, expression of parkin suppressed these mitochondrial dysfunctions. Our results indicate parkin as a neuroprotective regulator of FUS‐induced proteinopathy by recovering the protein levels of mitochondrial complexes I and III. Our findings on parkin‐mediated neuroprotection may expand our understanding of FUS‐induced ALS pathogenesis.

中文翻译：

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Parkin的表达逆转了在肉瘤引起的肌萎缩性侧索硬化症中融合的线粒体功能障碍。

融合在肉瘤（FUS）中的是与肌萎缩性侧索硬化症（ALS）和额颞叶变性相关的DNA / RNA结合蛋白。FUS导致神经毒性的确切分子机制尚未完全阐明。在这里，我们发现帕金森是果蝇中外源性人类野生型FUS诱导的缺陷表型的遗传抑制剂。。尽管Parkin的过表达不会调节FUS蛋白的表达水平，但是通过parkin的表达可以挽救表达FUS的幼虫和成年果蝇的机车缺陷。我们发现，肌肉组织中的FUS表达导致线粒体复合物I和III亚基的水平和组装减少，以及ATP降低。值得注意的是，parkin的表达抑制了这些线粒体功能障碍。我们的结果表明，帕金菌通过恢复线粒体复合体I和III的蛋白质水平，可作为FUS诱导的蛋白病的神经保护调节剂。我们对帕金森介导的神经保护作用的发现可能会扩展我们对FUS诱导的ALS发病机制的了解。