dc.contributor |
Háskóli Íslands |
dc.contributor |
University of Iceland |
dc.contributor.author |
Zhang, T. |
dc.contributor.author |
Zhou, Q. |
dc.contributor.author |
Ogmundsdottir, Margret H |
dc.contributor.author |
Möller, Katrin |
dc.contributor.author |
Siddaway, R. |
dc.contributor.author |
Larue, L. |
dc.contributor.author |
Hsing, M. |
dc.contributor.author |
Kong, S. W. |
dc.contributor.author |
Goding, C. R. |
dc.contributor.author |
Palsson, Arnar |
dc.contributor.author |
Steingrimsson, Eirikur |
dc.contributor.author |
Pignoni, F. |
dc.date.accessioned |
2020-02-24T10:14:30Z |
dc.date.available |
2020-02-24T10:14:30Z |
dc.date.issued |
2015-06-19 |
dc.identifier.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 |
dc.identifier.issn |
0021-9533 |
dc.identifier.issn |
1477-9137 (eISSN) |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/1545 |
dc.description |
Post-print (lokagerð höfundar) |
dc.description.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. |
dc.description.sponsorship |
This work was supported by the National Institutes of Health, National Eye Institute [grant number R01EY017097 to F.P.]; an RPB Unrestricted Grant and Lions District 20-Y1 award to the Dept. of Ophthalmology, SUNY-UMU (F.P.); the Icelandic Research Fund [grant numbers 130230-053 and 152715-051 to E.S.] a PHC Jules Verne 2014 grant [grant number 31891VM to E.S. and L.L.]; a grant from the Ligue Nationale Contre le Cancer (Equipe labellisee), INCa, Canceropole, Ile de France and Labex CelTisPhyBio [grant number ANR-11-LBX-0038 to L.L.]; and the Ludwig Institute for Cancer Research and the Harry J Lloyd Trust (to C.G.). |
dc.format.extent |
2938-2950 |
dc.language.iso |
en |
dc.publisher |
The Company of Biologists |
dc.relation.ispartofseries |
Journal of Cell Science;128(15) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
MITF, |
dc.subject |
TFEB |
dc.subject |
TORC1 |
dc.subject |
Gut |
dc.subject |
Melanocytes |
dc.subject |
v-ATPase |
dc.subject |
Ensím |
dc.subject |
Frumulíffræði |
dc.subject |
Gen |
dc.subject |
Meltingarfæri |
dc.title |
Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1 |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
CC BY 4.0 |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
Journal of cell science |
dc.identifier.doi |
10.1242/jcs.173807 |
dc.relation.url |
https://syndication.highwire.org/content/doi/10.1242/jcs.173807 |
dc.contributor.department |
Lífvísindasetur (HÍ) |
dc.contributor.department |
Biomedical Center (UI) |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.department |
Líf- og umhverfisvísindadeild (HÍ) |
dc.contributor.department |
Faculty of Life and Environmental Sciences (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |
dc.contributor.school |
Verkfræði- og náttúruvísindasvið (HÍ) |
dc.contributor.school |
School of Engineering and Natural Sciences (UI) |