Háskóli ÍslandsUniversity of IcelandZhang, T.Zhou, Q.Ogmundsdottir, Margret HMöller, KatrinSiddaway, R.Larue, L.Hsing, M.Kong, S. W.Goding, C. R.Palsson, ArnarSteingrimsson, EirikurPignoni, F.2020-02-242020-02-242015-06-19Zhang, T., Zhou, Q., Ogmundsdottir, M. H., Möller, K., Siddaway, R., Larue, L., . . . Pignoni, F. (2015). Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1. 128(15), 2938-2950. doi:10.1242/jcs.173807 Journal of Cell Science0021-95331477-9137 (eISSN)https://hdl.handle.net/20.500.11815/1545Post-print (lokagerð höfundar)The v-ATPase is a fundamental eukaryotic enzyme that is central to cellular homeostasis. Although its impact on key metabolic regulators such as TORC1 is well documented, our knowledge of mechanisms that regulate v-ATPase activity is limited. Here, we report that the Drosophila transcription factor Mitf is a master regulator of this holoenzyme. Mitf directly controls transcription of all 15 v-ATPase components through M-box cis-sites and this coordinated regulation affects holoenzyme activity in vivo. In addition, through the v-ATPase, Mitf promotes the activity of TORC1, which in turn negatively regulates Mitf. We provide evidence that Mitf, v-ATPase and TORC1 form a negative regulatory loop that maintains each of these important metabolic regulators in relative balance. Interestingly, direct regulation of v-ATPase genes by human MITF also occurs in cells of the melanocytic lineage, showing mechanistic conservation in the regulation of the v-ATPase by MITF family proteins in fly and mammals. Collectively, this evidence points to an ancient module comprising Mitf, v-ATPase and TORC1 that serves as a dynamic modulator of metabolism for cellular homeostasis.2938-2950eninfo:eu-repo/semantics/openAccessMITF,TFEBTORC1GutMelanocytesv-ATPaseEnsímFrumulíffræðiGenMeltingarfæriinfo:eu-repo/semantics/articleJournal of cell science10.1242/jcs.173807