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Intracellular pathways such as ERK and IRS2-AKT are highly regulated by stress and drugs of abuse and involved in regulation of mood-related disorders and drug-induced neuroplasticity 73,74

These enzymes include malic enzyme 1 (ME1) and IDH1, which generate NADPH, and thus the levels and subcellular compartmentalization of malate and isocitrate dictate the activity of these enzymes

CB-839 treatment increased mitochondrial SOX in both cell lines at relatively low concentrations, starting at 10 nM for the HG-3 cell line and 100 nM for the MEC-1 cell line

As described previously, the major part of exogenous cystine is incorporated in GSH, yet unexpectedly, the remaining part is incorporated in co-enzyme A synthesis via the pantothenate pathway (69)

However, the rapid onset of depletion suggests the involvement of additional mechanisms

For the grayscale pretreatment image, yellow arrowhead points at the outer epithelial tent, blue dots represent incurrent canals, and red dots represent excurrent canals