Fig. 5: | Nature Communications

Fig. 5

From: Fibril formation and therapeutic targeting of amyloid-like structures in a yeast model of adenine accumulation

Fig. 5

TA rescues salvage model yeast by preventing adenine assembly into toxic amyloid-like structures. a WT and aah1Δapt1Δ cells diluted to OD600 0.01 were grown in SD media in the presence of adenine. 0.5 mM TA was added to the samples at different OD600 values (0.01, 0.05, 0.1, and 0.2). *P < 0.01 (Student’s t-test). The percentage of growth represents the growth with TA compared to the growth without TA. Values are the mean ± s.d. of three experiments. Schematic illustrations of adenine assembly inside the cells at the different OD600 values following the addition of TA are shown below the X-axis. b Intracellular concentration of adenine determined using GC–MS. WT and aah1Δapt1Δ cells were grown in SD media in the presence of adenine, with or without 0.5 mM TA, and the metabolites were extracted. ns, not significant (Student’s t-test). Values are the mean ± s.d. of three experiments. c Schematic model of adenine accumulation in WT cells compared to the adenine salvage model in the absence or presence of adenine, and following the addition of the TA inhibitor. The model reflects the relative amounts of the metabolite as determined experimentally. Upon feeding of the salvage mutant with adenine, the metabolite accumulates into ordered assemblies. Administration of the inhibitor, as recently shown by an in vitro study15, prevents the formation of assemblies at the nucleation phase, without any significant effect on the total concentration of the metabolite