PINK1 and Parkin: emerging themes in mitochondrial homeostasis

Abstract

The Parkinson's disease (PD)-associated protein kinase, PTEN-induced putative kinase1 (PINK1), and ubiquitin E3 ligase Parkin, function in a common signalling pathway known to regulate mitochondrial network homeostasis and quality control, including mitophagy. The multistep activation of this pathway, as well as an unexpected convergence between the post-translational modifications of ubiquitylation and phosphorylation, has added breadth to our understanding of cellular damage responses during human disease. In concert with these new insights in signal transduction, unique modalities and signatures of vertebrate mitophagy have been unravelled in vivo for the very first time. The cell biology of mammalian mitophagy, and the roles of PINK1-Parkin signalling in vivo have emerged to be more complex than previously thought.