Using this inducible cardiac-specific Ampkα2 knockout mouse model, we show that specific cardiac deficiency of AMPKα2 at adult age in males (1) did not induce cardiac hypertrophy; (2) led to a mild left ventricular dysfunction; (3) resulted in the development of cardiac fibrosis; (4) reduced complex I-driven respiration without changes in mitochondrial mass or in in vitro complex I activity; (5) was associated with a rearrangement of the CL species and a reduced integration of complex I into the ETC supercomplexes. The gene discussed is PRKAA2; the disease is cardiac hypertrophy.