Fig. 2

Schematic representation of the mitochondrial and oxidative stress pathways affected in Parkinson disease. Mutations in parkin, PINK1, DJ-1 and FBXO7 have been associated with autosomal recessive Parkinsonian syndromes. a In healthy, polarized mitochondria (∆Ψm) PINK1 translocates at the inner mitochondrial membrane via the mitochondrial import receptor TOMM20 machinery, which subsequently results in the degradation of PINK1. In damaged, depolarized mitochondria (∆Ψm↓), PINK1 accumulates at the outer mitochondrial membrane and recruits parkin upon phosphorylation. Moreover, parkin mediates the degradation of the parkin interacting substrate (PARIS), a repressor of the PGC1α transcriptional coactivator, leading to nuclear translocation of PGC1α and transcriptional activation of mitochondria associated genes. b In oxidative stress conditions or ∆Ψm↓, DJ-1 p.Cys106 will form a sulfonic acid, which will activate DJ-1 to regulate transcription of antioxidant genes and to promote mitophagy. c FBXO7 is a subunit of the SKP1-cullin-F-box (SCF) complex. PINK1 is involved in the recruitment of FBXO7 to damaged mitochondria which in turn leads to the recruitment of parkin