We previously demonstrated that genetic or pharmacological inhibition of InsP3R or MCU in tumorigenic cancer cell lines and normal counterparts decreased cellular ATP content, increased NAD+/NADH ratio, reduced cell proliferation and activated mTOR-independent autophagy as a cell survival mechanism (Cardenas et al., 2010; Cardenas et al., 2016), emphasizing the importance of ER-to-mitochondria Ca2+ transfer to support basal metabolic requirements. The gene discussed is MCU; the disease is cancer.