Editors' ChoiceTOLERANCE

Stress, Flies, and Ethanol Tolerance

Science's STKE  16 Aug 2005:
Vol. 2005, Issue 297, pp. tw298
DOI: 10.1126/stke.2972005tw298

Like mammals, Drosophila develop tolerance to alcohol: A fly exposed to ethanol a second time needs to absorb more ethanol before it loses postural control than does a naïve fly. Scholz et al. screened mutant flies for aberrant tolerance to ethanol and identified a strain, AE10, that showed a normal response to the initial exposure to ethanol but decreased ability to develop tolerance. The phenotype resulted from disruption of a new gene, hangover (hang), which was expressed in neurons throughout the nervous system and encoded a nuclear zinc finger protein with a predicted calcium-binding EF hand. Having previously shown that flies that do not synthesize the neuromodulator octopamine (Tbh flies) also exhibit decreased ethanol tolerance, the authors investigated the effect on ethanol tolerance of the combined loss of octopamine and HANG. Tbh hangAE10 double mutants completely lost ethanol tolerance, which suggests that octopamine and HANG function in parallel pathways. Moreover, heat stress induced cross-tolerance to ethanol in wild-type flies, an effect that was substantially reduced in hangAE10 flies but not in Tbh flies. hangAE10 flies but not Tbh flies were also more sensitive than wild-type flies to oxidative stress (determined by survival following exposure to different concentrations of paraquat). Thus, the authors conclude that HANG defines a cellular stress pathway involved in the development of tolerance to ethanol that functions in parallel with the tolerance pathway involving octopamine, which is independent of cellular stress.

H. Scholz, M. Franz, U. Heberlein, The hangover gene defines a stress pathway required for ethanol tolerance development. Nature 436, 845-847 (2005). [PubMed]