Titill: | Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1 |
Höfundur: |
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Útgáfa: | 2015-06-19 |
Tungumál: | Enska |
Umfang: | 2938-2950 |
Háskóli/Stofnun: | Háskóli Íslands University of Iceland |
Svið: | Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) Verkfræði- og náttúruvísindasvið (HÍ) School of Engineering and Natural Sciences (UI) |
Deild: | Lífvísindasetur (HÍ) Biomedical Center (UI) Læknadeild (HÍ) Faculty of Medicine (UI) Líf- og umhverfisvísindadeild (HÍ) Faculty of Life and Environmental Sciences (UI) |
Birtist í: | Journal of Cell Science;128(15) |
ISSN: | 0021-9533 1477-9137 (eISSN) |
DOI: | 10.1242/jcs.173807 |
Efnisorð: | MITF,; TFEB; TORC1; Gut; Melanocytes; v-ATPase; Ensím; Frumulíffræði; Gen; Meltingarfæri |
URI: | https://hdl.handle.net/20.500.11815/1545 |
Tilvitnun:Zhang, 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 Science
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Útdráttur: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.
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Athugasemdir:Post-print (lokagerð höfundar)
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Leyfi:CC BY 4.0
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