Regulation of Mitochondrial Proliferation by PGC-1α Induces Cellular Apoptosis in Musculoskeletal Malignancies

A number of studies have reported that decreased mitochondrial numbers are linked with neoplastic transformation and/or tumor progression, including resistance to apoptosis. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a multi-functional transcriptional coactivator that regulates the activities of multiple nuclear receptors and transcriptional factors involved in mitochondrial biogenesis. In this study, we observed that the number of mitochondria in sarcoma tissues, such as osteosarcoma and malignant fibrous histiocytoma, is significantly lower than that in normal muscle tissue or benign tumors, and that increasing the number of mitochondria by PGC-1a overexpression induces mitochondrial apoptosis in human sarcoma cell lines. The findings suggest that decreased mitochondrial numbers may contribute to musculoskeletal tumor progression, and that regulation of mitochondrial numbers by PGC-1a could be a potent therapeutic tool for human malignancies.