These phosphorylation marks are the triggering signals that lead to FOXO3a translocation into the mitochondrial matrix, where it binds to mtDNA together with TFAM, mtRNA polymerase, and SIRT3, and activates the expression of mitochondrial oxidative phosphorylation (OXPHOS) genes involved in sustaining and re-establishing the normal energetic state of mitochondria in metabolically stressed cancer cells. The gene discussed is FOXO3; the disease is cancer.