Unexpectedly as well, the canonical mt-ISR based on eIF2α phosphorylation did not precede but followed the c-MYC upregulation (Fig. 8a), suggesting that mt-ISR is downstream of c-MYC, analogous to c-MYC-driven excessive anabolic metabolism leading to integrated stress response in cancer cells68. The gene discussed is EIF2A; the disease is cancer.