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Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1

Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1


Title: Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1
Author: Zhang, T.
Zhou, Q.
Ogmundsdottir, Margret H   orcid.org/0000-0003-2836-9988
Möller, Katrin   orcid.org/0000-0002-4720-8568
Siddaway, R.
Larue, L.
Hsing, M.
Kong, S. W.
Goding, C. R.
Palsson, Arnar   orcid.org/0000-0002-6525-8112
... 2 more authors Show all authors
Date: 2015-06-19
Language: English
Scope: 2938-2950
University/Institute: Háskóli Íslands
University of Iceland
School: Heilbrigðisvísindasvið (HÍ)
School of Health Sciences (UI)
Verkfræði- og náttúruvísindasvið (HÍ)
School of Engineering and Natural Sciences (UI)
Department: Lífvísindasetur (HÍ)
Biomedical Center (UI)
Læknadeild (HÍ)
Faculty of Medicine (UI)
Líf- og umhverfisvísindadeild (HÍ)
Faculty of Life and Environmental Sciences (UI)
Series: Journal of Cell Science;128(15)
ISSN: 0021-9533
1477-9137 (eISSN)
DOI: 10.1242/jcs.173807
Subject: MITF,; TFEB; TORC1; Gut; Melanocytes; v-ATPase; Ensím; Frumulíffræði; Gen; Meltingarfæri
URI: https://hdl.handle.net/20.500.11815/1545

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Citation:

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

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.

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Post-print (lokagerð höfundar)

Rights:

CC BY 4.0

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