The study investigates the role of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) in cardiac mitochondrial biogenesis and function. PGC-1 gene expression is induced in the mouse heart after birth and during short-term fasting, conditions that increase cardiac mitochondrial energy production. In cultured cardiac myocytes, forced PGC-1 expression induces the expression of nuclear and mitochondrial genes involved in mitochondrial energy pathways, increases mitochondrial number, and stimulates coupled respiration. In transgenic mice with cardiac-specific overexpression of PGC-1, uncontrolled mitochondrial proliferation leads to sarcomeric disruption and dilated cardiomyopathy. These findings identify PGC-1 as a critical regulator of cardiac mitochondrial number and function, linking mitochondrial biogenesis to energy production in the heart.The study investigates the role of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) in cardiac mitochondrial biogenesis and function. PGC-1 gene expression is induced in the mouse heart after birth and during short-term fasting, conditions that increase cardiac mitochondrial energy production. In cultured cardiac myocytes, forced PGC-1 expression induces the expression of nuclear and mitochondrial genes involved in mitochondrial energy pathways, increases mitochondrial number, and stimulates coupled respiration. In transgenic mice with cardiac-specific overexpression of PGC-1, uncontrolled mitochondrial proliferation leads to sarcomeric disruption and dilated cardiomyopathy. These findings identify PGC-1 as a critical regulator of cardiac mitochondrial number and function, linking mitochondrial biogenesis to energy production in the heart.