To investigate this issue, we adopted a genetic approach in which we used a unique human osteosarcoma cell line, C4T, which carries a homoplasmic shift mutation in the mitochondrial gene encoding the ND4 subunit of NADH dehydrogenase, causing the abrogation of Complex I of the mitochondrial ETC; this prevents oxidative ATP production. The gene discussed is ENSG00000251605; the disease is osteosarcoma.