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GSK3b regulates mitochondrial energy metabolism. Inhibition of GSK3b by lithium stabilizes PGC1a and increases mitochondrial respiration. Activated PGC1a increases expression of target genes coincident with increased respiration. GSK3 negatively regulates AMPK and activating phosphorylation of AMPK is increased with lithium. These nutrient sensing pathways converge on mitochondrial function, suggesting that GSK3 is a key upstream regulator of metabolism
