Even if these results are in contrast with the SIRT3-dependent activation of TRAP1 observed in GSC (Park et al., 2019), they provide a glimpse into a fascinating scenario in which SIRT3 and TRAP1 can harmonize the bioenergetic features of tumor cells with their needs and supplies, and provide a regulatory backbone that dynamically interacts with key metabolic components. The gene discussed is TRAP1; the disease is neoplasm.