In this study the role of the sirtuins family members SIRT1, SIRT3, and SIRT5 in the regulation of autophagy was analyzed in the human osteosarcoma U2OS, and mesothelioma Mero-14 and REN cells treated with the inhibitor of the complex I of the mitochondrial respiratory chain rotenone, the topoisomerase II inhibitor etoposide widely used in the clinic, and the sirtuins activator and autophagy modulator resveratrol. The gene discussed is SIRT1; the disease is osteosarcoma.