Transducers of Regulated CREB (TORCs) are a recently characterized family of coactivators that enhance CRE-dependent transcription by interacting with the cAMP and calcium responsive transcription factor, CREB. TORC has been shown to mediate the CREB-regulated transcription program of gluconeogenic genes in the mammalian liver. In response to fasting signals, TORC is dephosphorylated and transported to the nucleus where it binds CREB and activates transcription. Feeding promotes the phosphorylation and degradation of TORC through insulin signaling. We have found that Drosophila possess a single member of this family (dTORC) that behaves identically to its mammalian counterparts. In order to investigate the physiological role of TORC in an intact organism, we created TORC-null mutant flies. These animals display reduced glycogen and lipid stores and are sensitive to starvation and oxidative stress. Remarkably, neuronal expression of dTORC can rescue these phenotypes, suggesting the existence of an unknown pathway in the brain that controls metabolic stress resistance. dTORC mutant flies also display profound cardiac pathology that can be reversed by expression of dTORC in the heart, but not in neurons. These results suggest that TORC may function in many physiological processes beyond metabolic control. This work represents the first description of a completely TORC-null organism.