Genome-wide RNAi screen identifies the Parkinson disease GWAS risk locusSREBF1as a regulator of mitophagy
Copyright policy )Genome-wide RNAi screen identifies the Parkinson disease GWAS risk locusSREBF1as a regulator of mitophagy
SignificanceThis study presents the first results, to our knowledge, of a whole-genome RNAi screen to identify factors that promote Parkin-mediated mitophagy, which have been validated for conservation across species. Top hits comprise several components of thesterol regulatory element binding transcription factor(SREBF) lipogenesis pathway, and we show that provision of exogenous lipids can promote the mitophagy pathway. BecauseSREBF1has been identified as a risk locus for sporadic Parkinson disease (PD) through genome-wide association studies, the identification ofSREBF1in our screen provides evidence for mechanistic insight into the pathogenesis of sporadic PD. Thus, our functional studies provide the first insight, to our knowledge, into why the master regulator for lipogenesis,SREBF1, may contribute to sporadic PD and further underscore the impact of dysfunctional mitophagy on pathogenesis.
- University of Geneva Switzerland
- University of Padua Italy
- University of Sheffield United Kingdom
Membrane Potential, Mitochondrial, F-Box-WD Repeat-Containing Protein 7, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, F-Box Proteins, Immunoblotting, Mitophagy, Cell Cycle Proteins, Parkinson Disease, Cell Line, Mitochondria, Drosophila melanogaster, Gene Expression Regulation, Animals, Drosophila Proteins, Humans, RNA Interference, Protein Kinases, Genome-Wide Association Study, HeLa Cells
Membrane Potential, Mitochondrial, F-Box-WD Repeat-Containing Protein 7, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, F-Box Proteins, Immunoblotting, Mitophagy, Cell Cycle Proteins, Parkinson Disease, Cell Line, Mitochondria, Drosophila melanogaster, Gene Expression Regulation, Animals, Drosophila Proteins, Humans, RNA Interference, Protein Kinases, Genome-Wide Association Study, HeLa Cells
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