DJ-1 and ATP synthase are required for local protein synthesis in midbrain dopaminergic neurons

Dopaminergic neurons have extensive neuritic arbors therefore local protein synthesis is required. Familial PD risk gene PARK-7 (DJ-1) is a key regulator of ATP synthase and of dopaminergic growth and survival. We now find that inhibition of ATP synthase function completely abrogates protein synthesis in dopaminergic (mesDA) neuronal processes, and we demonstrate that DJ-1 is an mRNA binding protein for F1FO ATP synthase β subunit mRNA. DJ-1 localizes ATP β mRNA into neurites, thus DJ-1 patient fibroblasts and DJ-1-/- mesDA mouse neurons have low ATP β mRNA and protein, reduced growth and low protein synthesis rates. Over-expression of ATP β rescues these defects. We conclude that DJ-1 is required to optimize the stoichiometric structure of the ATP synthase in the neuritic arbors. This supports the local protein synthesis required for normal neuritic growth.