Clk1 deficiency promotes neuroinflammation and subsequent dopaminergic cell death through regulation of microglial metabolic reprogramming

Highlights • Clock (Clk)1/COQ7 is a mitochondrial hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q or UQ). • Reduced expression of Clk1 in microglia enhanced the LPS-induced proinflammatory response and promoted aerobic glycolysis. • Inhibition of glycolysis abolished Clk1 deficiency-induced hypersensitivity to the inflammatory stimulation. • mTOR/HIF-1α and ROS/HIF-1α signaling pathways are involved in Clk1 deficiency-induced aerobic glycolysis. • Exaggerated expressions of proinflammatory genes and loss of DA neurons were observed in Clk1+/- mice in MPTP induced mouse model of Parkinson’s disease.