Abstract

PINK1 is a mitochondria-targeted kinase, whose mutations are a cause of Parkinson's disease. We set out to better understand PINK1's effects on mitochondrial proteinsin vivoUsing an unbiased phosphoproteomic screen inDrosophila, we found that PINK1 mediates the phosphorylation of MCAD, a mitochondrial matrix protein critical to fatty acid metabolism. By mimicking phosphorylation of this protein in aPINK1null background, we restoredPINK1null's climbing, flight, thorax, and wing deficiencies. Due to MCAD's role in fatty acid metabolism, we examined the metabolic profile ofPINK1null flies, where we uncovered significant disruptions in both acylcarnitines and amino acids. Some of these disruptions were rescued by phosphorylation of MCAD, consistent with MCAD's rescue ofPINK1null's organismal phenotypes. Our work validates and extends the current knowledge of PINK1, identifies a novel function of MCAD, and illuminates the need for and effectiveness of metabolic profiling in models of neurodegenerative disease.

View details for PubMedID 29563254