Fig. 4. Succinate and glycine secretion caused by isocitrate lyase activity increases non-replicating survival.

(A) 10 top hits of predicted metabolic pathways leading to succinate secretion. The numbers depict the rank of the probability scores of shown metabolic pathways leading to secreted succinate. The absolute scores are represented by the arrow size (Table S2). (B) [U-¹³C]-citrate feeding experiment and tracing of the labeling in the endo- and exometabolome. The fraction of each mass isomer in the total pool of intracellular metabolites is indicated by different colors. (C) Disruption of the isocitrate lyase genes (Δicl1 Δicl2) impairs both uptake of citrate and secretion of succinate. (D) [U-13C]-glycine secretion upon [U-¹³C]-citrate feeding depends on isocitrate lyase activity (E) Fitness upon resuscitation of wild-type and the Δicl1/2 strain after different times under hypoxic conditions. A minimum of three independent biological experiments was performed for each plot and untargeted measurements were performed in two technical replicates.