A mechanistic review of Parkin activation

Parkin and phosphatase tensin homolog (PTEN)-induced kinase 1 (PINK1) constitute a feed-forward signalling pathway that mediates autophagic removal of damaged mitochondria (mitophagy). With over 130 mutations identified to date in 1000 patients with early onset parkinsonism, is considered hot spot pathways involved PD aetiology. an E3 ligase how its activity regulated has been extensively studied: inter-domain interactions exert tight inhibition on activity; binding phospho-ubiquitin relieves this auto-inhibition; phosphorylation shifts the equilibrium towards maximal activation. This review focusses recent, structural findings regulation activity. What follows mechanistic introduction family ligases includes Parkin, followed by brief description elements unique lock enzyme autoinhibited state, contrasted emerging models have shed light possible mechanisms