ATP13A2 regulates mitochondrial bioenergetics through macroautophagy

► Mutations in the ATP13A2 gene cause autosomal recessive parkinsonism with dementia. ► ATP13A2 RNAi increases mitochondria mass and fragmentation in neurons and SH-SY5Y cells. ► Cells consume more oxygen to maintain cellular ATP, while producing increased ROS. ► ATP13A2 deficiency reduces basal autophagic flux and increases phospho-mTOR. ► Loss of this lysosomal P-type ATPase adversely affects autophagic quality control.