PINK1: from enzymatic function to modeling Parkinson’s disease
Scarffe, Leslie A
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The loss of PTEN-Induced Kinase 1 (PINK1) is the second most common cause of autosomal recessive Parkinson’s disease. PINK1 has been shown to play an important role in mitochondrial quality control by regulating the function of Parkin, an E3 ubiquitin ligase also linked to autosomal recessive Parkinson’s disease. Aside from its regulation of Parkin, the role of PINK1 phosphorylation is not yet well understood and very few PINK1 substrates are known. Here, we identified 204 in vitro PINK1 substrates by using protein microarrays. Characterization of the PINK1 phosphorylome yielded novel substrates that suggest that PINK1 may play an even broader role in the regulation of cellular ubiquitination than previously understood. We also identified a novel way in which PINK1 may modulate Parkin ubiquitination activity. Furthermore, we have established novel human dopaminergic neuron models of loss of PINK1. Characterizing these cells will further our understanding of the pathogenesis of Parkinson’s disease in a disease-relevant model system.