Fig. 7: Model of ATF4-dependent and ATF4-independent ISR metabolic outputs. | Nature Communications

Fig. 7: Model of ATF4-dependent and ATF4-independent ISR metabolic outputs.

From: Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis

Fig. 7

The ISR increases glutathione and serine synthesis, while diverting glucose and glutamine carbon away from oxidation in mitochondria. Synthesis of aspartate, asparagine and acyl-CoA is maintained via reductive carboxylation of glutamine. These ATF4-dependent changes are accompanied by ATF4-independent inhibition of glycolysis, increased pentose phosphate pathway activity, and increased TG production and accumulation in lipid droplets. Changes in pathway utilization, metabolite abundance and enzyme expression are indicated by color (red = up, blue = down).

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