(A) β2−/− mice, a model of unopposed physiologic-level β1-AR signaling, show dramatic mitochondrial fragmentation with increased number and decreased area and perimeter versus WT littermates (n=3–5/group). (B) Drp1 mitochondrial translocation was increased and PINK1 was decreased in sedentary β2−/− (n=3/group). (C) Despite marked mitochondrial fragmentation, β2−/− mice had normal baseline respiration by Oroboros oxygraph normalized to 50μg of mitochondria (n=4/group). (D) β2−/− mice have enhanced exercise running time, distance and work, which is blocked with β1-AR inhibition by metoprolol (n=8/group).