Moreover, as the mitochondrial UPR has been associated with ISR activation, a focused look at key mitochondrial UPR members, including HSPA9, HSPD1, HSPE1, and LONP1, confirmed coordinated upregulation of this pathway in HCC (Fig. 2F, middle; refs. 33, 34). This evidence concerns the gene HSPA9 and hepatocellular carcinoma.