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PGC-1α integrates signals from several important upstream enzymes such as cAMP (through PKA and CREB phosphorylation), cGMP (through NO), AMPK, Ca 2+ (through CaMK), MEF-2 (through Calcineurin A) and p38 MAPK, and exerts direct control over transcription of the nucleus-encoded respiratory subunits and indirect control of the mitochondrial subunits