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Zhang, T., Zhou, Q., Ogmundsdottir, M.H., Möller, K., Siddaway, R., Larue, L., Hsing, M., Kong, S.W., Goding, C.R., Palsson, A., Steingrimsson, E., Pignoni, F. (2015). Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1.  J. Cell Sci. 128(15): 2938--2950.
FlyBase ID
FBrf0229222
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC4540953 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Sci.
    Title
    Journal of Cell Science
    Publication Year
    1966-
    ISBN/ISSN
    0021-9533
    Data From Reference
    Aberrations (1)
    Alleles (64)
    Genes (103)
    Sequence Features (3)
    Natural transposons (1)
    Insertions (10)
    Experimental Tools (6)
    Transgenic Constructs (37)