Protein network analysis links the NSL complex to Parkinson's disease via mitochondrial & nuclear biology

This online depository corresponds to manuscript : Protein network analysis links the NSL complex to Parkinson’s disease via mitochondrial & nuclear biology.

Authors: Katie Kelly, Patrick A. Lewis, Helene Plun-Favreau, Claudia Manzoni

Whilst the majority (~90-95%) of PD cases are sporadic, much of our understanding of the pathophysiological basis of disease can be traced back to the study of rare, monogenic forms of disease. However, in the past decade, the availability of Genome-Wide Association Studies (GWAS) has facilitated a shift in focus, toward identifying common risk variants conferring an increased risk of developing PD across the population. 

A recently developed mitophagy screening assay of GWAS candidates, has functionally implicated the non-specific lethal (NSL) complex, a chromatin remodeler, in the regulation of PINK1-mitophagy. Here, a bioinformatics approach has been taken to investigate the interactome of the NSL complex, to unpick its relevance to PD progression. The mitochondrial interactome of the NSL complex has been built, mining 3 separate repositories: PINOT, HIPPIE and MIST, for curated, literature-derived protein-protein interaction (PPI) data. A multi-layered approach has been taken to; i) build the ‘mitochondrial’ NSL interactome, applying PD gene-set enrichment analysis to explore the relevance of the NSL mitochondrial interactome to PD and, ii) build the PD-oriented NSL interactome, using functional enrichment, to uncover biological pathways underpinning the NSL /PD association.