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• W2100570106 abstract "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." @default.
• W2100570106 created "2016-06-24" @default.
• W2100570106 creator A5002433296 @default.
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• W2100570106 date "2015-01-01" @default.
• W2100570106 modified "2023-10-17" @default.
• W2100570106 title "Mitf is a master regulator of the v-ATPase forming an Mitf/v-ATPase/TORC1 control module for cellular homeostasis" @default.
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• W2100570106 doi "https://doi.org/10.1242/jcs.173807" @default.
• W2100570106 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4540953" @default.
• W2100570106 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26092939" @default.
• W2100570106 hasPublicationYear "2015" @default.
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