Loss of PINK1 causes age-dependent mitochondrial trafficking deficits in nigrostriatal dopaminergic neurons via aberrant p38 MAPK activation (opens in new tab)

Mutations in PTEN-induced putative kinase 1 (PINK1) cause early-onset, autosomal-recessive Parkinson’s disease (PD). While previous studies have shown age-related declines in dopamine release and ATP levels in Pink1−/− mice, the mechanisms remain unclear. Using a novel TH-Mito-Dendra2 transgenic mouse model to label dopaminergic neuron mitochondria, we show that PINK1 loss leads to age-dependent defects in axonal mitochondrial trafficking in acute brain slices. These deficits are characterize...