Hypothesized model. STAT3 is phosphorylated at Y705, which signals its localization to the nucleus to regulate the expression of several genes, including MYC. MYC, in turn, promotes expression of the amino acid transporter SLC1A5, allowing influx of glutamine into the cell and, ultimately, abundance of TCA cycle intermediates and GSH. TCA cycle intermediates then promote OXPHOS by ETC activity. GSH is known to promote glutathionylation of the ETC complex II, which is important for its activity. Upon inhibition of STAT3, glutaminolysis is compromised, decreasing levels of glutamate, GSH, and TCA cycle intermediates, thereby decreasing OXPHOS in LSCs.