Fig. 3

JAK inhibitors modify STAT3 signalling in motor neurons. a Under constant stimulation, STAT3pY705 accumulates in the nucleus, maintaining the expression of glycolytic enzymes but reducing the provision of mitoSTAT to the mitochondrial ETC, resulting in reduced oxidative phosphorylation and thus reduced ATP provision. b JAK inhibition reduces STAT3pY705, increases the provision of mitoSTAT3 to the mitochondrial ETC, thereby increasing oxidative phosphorylation and resulting in increased ATP generation. ERK, extracellular signal-related kinase; ETC, electron transport chain; GRIM-19, genes associated with retinoid–IFN-induced mortality-19; JAK, Janus kinase; LDH, lactate dehydrogenase; mitoSTAT, mitochondrial STAT3; PDH, pyruvate dehydrogenase; STAT3, Signal transducer and activator of transcription 3