In heart failure models, a pathological shift from AMPKα2 to AMPKα1 impairs mitophagy and exacerbates mitochondrial dysfunction, whereas restoration of AMPKα2 enhances mitophagy via the PINK1/Parkin pathway and reduces ROS, effects that are lost in PINK1/Parkin-deficient systems (98). The gene discussed is PRKAA2; the disease is heart failure.