Fig. 4. Increased Rheb-TOR signaling in muscle but not in neurons or fat bodies sensitizes adult flies to oxidative stress. (A) Overexpression of Rheb in neurons using the pan-neural driver, elav-GAL4 and the inducible (with RU486) GeneSwitch (GS) elav GS-GAL4 does not sensitize flies to oxidative stress. (B) In addition, overexpression of Rheb in the fat bodies with lsp2-GAL4 or DJ634-GAL4 does not sensitize flies to oxidative stress. Similarly, using the GeneSwitch S106 GS-GAL4, which allows expression in the abdominal fat body does not sensitize flies to oxidative stress. All values reported in A-C represent the mean survival of the indicated genotype 24 hours after exposure to 5% H₂O₂. (C) By contrast, flies overexpressing Rheb in muscle tissue (fed RU486) using the pan-muscle Gene Switch (GS) driver, myosin heavy chain (MHC) GS-GAL4 are sensitive to oxidative stress compared with control MHC GS>Rheb flies (not fed RU486). At 24 hours, the mean survival of MHC GS>Rheb flies not fed RU486 (n=102) is 90% whereas it is only 54% for MHC GS>Rheb flies fed RU486 (n=96, P=0.0084) (C). (D) A Kaplan-Meier survival plot further reveals the sensitivity of MHC GS>Rheb +RU flies to oxidative stress compared with MHC GS>Rheb –RU flies. Error bars represent the s.d. Statistical comparison (T-test): all P values are based on comparison of flies fed RU486 with those not fed RU486.