FIGURE 1 | Reduced extracellular Ado transport and receptor suppress mHTT induced lethality. (A,B) Relative level of extracellular Ado (A) and ATP (B) titers in Q93-expressing (da > Q93), Q20-expressing (da > Q20), and control da -GAL4 (da/+) larvae. Ado and ATP concentration are normalized to control larvae. Significance was analyzed by ANOVA; significant differences ( P < 0.05) among treatment groups are marked with different letters; N.S., not significant; n = 6. Error bars are presented as mean ± SEM. (C) Transcription levels of genes involved in regulating Ado homeostasis in Q93-expressing (elav > Q93) and control Q20-expressing (elav > Q20) larval brains. Significance was analyzed by Student’s t -test and labeled as follows: * P < 0.05, ** P < 0.01, *** P < 0.001; N.S., not significant. n = 3. Error bars are presented as mean ± SEM. (D) Eclosion rate of mHTT-expressing adult females (elav > Q93) with RNAi silencing (Ri) Ado metabolic enzymes, transporters, adoR , and control gfp . Numbers below each column indicate the number of replicates (n). Significance was analyzed by ANOVA; significant differences ( P < 0.05) among treatment groups are marked with different letters. (E) Survival of mHTT-expressing adult females (elav > Q93) with RNAi silencing (Ri) Ado metabolic enzymes, transporters, adoR , and control gfp . Significance was analyzed by weighted log-rank test; significant differences between each treatment group and control ( gfp -Ri) are labeled as follows: *** P < 0.001; N.S., not significant. n > 200. (F) Survival of mHTT-expressing adult females (elav > Q93) overexpressing (Ox) Ado metabolic enzymes ( adgf-A and adenok ), transporters ( ent2 ), adoR , and control gfp . Significance was analyzed by a weighted log-rank test; significant differences between each treatment group to control ( gfp -Ri) are labeled as *** P < 0.001. n > 200.