Fig. 11

Schematic of IFI6-modulated ROS generation in ESCC cells. (Left panel) In IFI6_low ESCC cells, mitochondrial supercomplex formation is suppressed, leading to OXPHOS deficiency and subsequent mitochondrial ROS overproduction, which in turn causes mitochondrial calcium overload. The ATP shortage resulting from insufficient OXPHOS induces ER stress, leading to the upregulation of ATF3 expression and the transcriptional activation of NOX4, which enhances ER-mediated ROS production. All of these mechanisms ultimately cause oxidative stress. Elevated ROS levels suppress tumor cell proliferation and induce apoptosis. (Right panel) In IFI6^high ESCC cells, undisturbed mitochondrial supercomplex assembly allows for stable mitochondrial calcium influx, optimal mitochondrial function, and inhibition of ER stress. Under these conditions, mitochondria and NOX4 produce low or moderate levels of ROS, which can be eliminated by cellular antioxidants, ultimately promoting cancer cell proliferation and suppressing cell apoptosis