Published in

National Academy of Sciences, Proceedings of the National Academy of Sciences, 2(115), 2017

DOI: 10.1073/pnas.1711023115

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Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

Significance In mitophagy, damaged mitochondria are targeted for disposal by the autophagy machinery. PARKIN promotes signaling of mitochondrial damage to the autophagy machinery for engagement, and PARKIN mutations cause Parkinson’s disease, possibly because damaged mitochondria accumulate in neurons. Because regulation of PARKIN abundance and the impact on signaling are poorly understood, we performed a genetic screen to identify PARKIN abundance regulators. Both positive and negative regulators were identified and will help us to further understand mitophagy and Parkinson’s disease. We show that some of the identified genes negatively regulate PARKIN gene expression, which impacts signaling of mitochondrial damage in mitophagy. This link between transcriptional repression and mitophagy is also apparent in neurons in culture, bearing implications for disease.