蛋白质网络分析通过线粒体和核生物学将NSL复合体与帕金森病联系起来

IF 3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular omics Pub Date : 2023-06-14 DOI:10.1039/D2MO00325B
Katie Kelly, Patrick A. Lewis, Helene Plun-Favreau and Claudia Manzoni
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引用次数: 0

摘要

虽然大多数帕金森病(PD)病例是散发性的,但我们对该疾病的病理生理基础的了解可以追溯到对罕见的单基因帕金森病的研究。在过去的十年中,全基因组关联研究(GWAS)的可用性促进了焦点的转移,转向识别在人群中增加患帕金森病风险的常见风险变异。最近的一项GWAS候选细胞的线粒体自噬筛选实验在功能上暗示了非特异性致死(NSL)复合物在调节pink1 -线粒体自噬中的作用。本文采用生物信息学方法研究NSL复合物的蛋白质组,以揭示其与PD发病机制的相关性。NSL相互作用组已经建立,使用3个在线工具:PINOT, HIPPIE和MIST,来挖掘精心策划的,文献衍生的蛋白质-蛋白质相互作用(PPI)数据。我们构建了(i)“线粒体”NSL相互作用组,探索其与PD遗传学的相关性;(ii) PD导向的NSL相互作用组,揭示NSL/PD关联的生物学途径。在本研究中,我们发现线粒体NSL相互作用组中PD相关基因的蛋白产物显著富集,包括孟德尔PD基因LRRK2和VPS35。此外,我们发现核过程是pd相关NSL相互作用组中最显著富集的过程之一。这些发现加强了NSL复合物在散发性和家族性PD中的作用,通过其线粒体和核功能介导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Protein network analysis links the NSL complex to Parkinson’s disease via mitochondrial and nuclear biology†

Protein network analysis links the NSL complex to Parkinson’s disease via mitochondrial and nuclear biology†

Whilst the majority of Parkinson’s Disease (PD) cases are sporadic, much of our understanding of the pathophysiological basis of the disease can be traced back to the study of rare, monogenic forms of PD. In the past decade, the availability of genome-wide association studies (GWAS) has facilitated a shift in focus, toward identifying common risk variants conferring increased risk of developing PD across the population. A recent mitophagy screening assay of GWAS candidates has functionally implicated the non-specific lethal (NSL) complex in the regulation of PINK1-mitophagy. Here, a bioinformatics approach has been taken to investigate the proteome of the NSL complex, to unpick its relevance to PD pathogenesis. The NSL interactome has been built, using 3 online tools: PINOT, HIPPIE and MIST, to mine curated, literature-derived protein–protein interaction (PPI) data. We built (i) the ‘mitochondrial’ NSL interactome exploring its relevance to PD genetics and (ii) the PD-oriented NSL interactome to uncover biological pathways underpinning the NSL/PD association. In this study, we find the mitochondrial NSL interactome to be significantly enriched for the protein products of PD-associated genes, including the Mendelian PD genes LRRK2 and VPS35. In addition, we find nuclear processes to be amongst those most significantly enriched within the PD-associated NSL interactome. These findings strengthen the role of the NSL complex in sporadic and familial PD, mediated by both its mitochondrial and nuclear functions.

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来源期刊
Molecular omics
Molecular omics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
5.40
自引率
3.40%
发文量
91
期刊介绍: Molecular Omics publishes high-quality research from across the -omics sciences. Topics include, but are not limited to: -omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance -omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets -omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques -studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field. Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits. Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.
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