The PGC-1a protein is a master regulator of mitochondrial biogenesis and oxidative metabolism. Accordingly, aberrant changes in the relative levels of PGC-1a in skeletal muscle or other tissues result in pathological consequences due to inadequate mitochondrial function. For example, mice that lack a functional PGC-1a gene in muscle display metabolic abnormalities and muscle damage, reminiscent of some of the symptoms of patients suffering from mitochondrial myopathies. In contrast, therapeutic elevation of PGC-1a in skeletal muscle of transgenic mice reduces muscle atrophy and ameliorates muscle wasting in COX10 knockout animals, a mouse model for a mitochondrial myopathy.