Figure 4. Inhibition of ATP synthase by α-KG causes conserved decrease in TOR pathway activity.
a, Decreased phosphorylation of mTOR substrates in U87 cells treated with octyl α-KG or oligomycin. Similar results were obtained in HEK-293, normal human fibroblasts, and MEFs (not shown). b, Increased autophagy in animals treated with α-KG or RNAi for atp-2 or CeTOR. c, GFP::LGG-1 puncta quantitated using ImageJ (Methods). 2–3 independent experiments. Bars indicate the mean. ****P < 0.0001; n.s., not significant (t-test, two-tailed, two-sample unequal variance). d, α-KG levels are increased in starved worms. **P < 0.01 (t-test, two-tailed, two-sample unequal variance). Mean ± s.d. is plotted. e, Model of α-KG-mediated longevity.