The PINK1–Parkin axis: An Overview

Parkin is a protein involved in familial Parkinson’s disease (PD), a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons. More than 20 years have passed since the discovery of Parkin; since that time, another familial PD protein has been identified: PINK1, which acts upstream of Parkin. PINK1 is a protein kinase that monitors mitochondrial integrity by sensing disability status, whereas Parkin is a ubiquitin–protein ligase that attaches ubiquitin chains to malfunctioning mitochondria as a degradation signal. Both enzymes cooperatively facilitate autophagic clearance of damaged mitochondria (also known as mitophagy). Collectively, the PINK1-Parkin axis functions as the core machinery for mitophagy in neurons, and deficiency in this pathway causes early-onset PD. In this review, I will discuss how the PINK1-Parkin study has progressed, with the personal episodes I have experienced.