Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy

Aleksander Aas; Pauline Isakson; Christian Bindesbøll; Endalkachew A Alemu; Arne Klungland; Anne Simonsen

doi:10.1371/journal.pone.0168182

Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy

PLoS One. 2017 Mar 13;12(3):e0168182. doi: 10.1371/journal.pone.0168182. eCollection 2017.

Authors

Aleksander Aas¹, Pauline Isakson¹, Christian Bindesbøll¹, Endalkachew A Alemu², Arne Klungland², Anne Simonsen¹

Affiliations

¹ Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
² Department of Molecular Microbiology A3.3021, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, Oslo, Norway.

Abstract

Polymorphic variants of the FTO (fat mass and obesity) gene associate with body mass index in humans, but the underlying molecular mechanisms have not been firmly determined. FTO is linked to energy homeostasis via amino acid sensing and is thought to activate the mammalian target of rapamycin complex 1, a negative regulator of autophagy. FTO localises both to the nucleus and the cytoplasm, and in this study we identify a functional nuclear localisation signal (NLS) in the N-terminus of FTO, as well as nuclear localization information in its very C-terminus. Inhibition of FTO nuclear transport has no effect on autophagy and in contrast to a previously proposed role of FTO in autophagy, we find no difference in starvation-induced autophagy in control cells compared to a panel of cell types depleted of FTO. Future studies that further characterise the cellular functions of FTO will be important to understand why variants in FTO are associated with body weight.

MeSH terms

Active Transport, Cell Nucleus*
Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
Alpha-Ketoglutarate-Dependent Dioxygenase FTO / metabolism*
Animals
Autophagy*
Gene Knockdown Techniques
Humans
Mice
Mice, Inbred C57BL
Nuclear Localization Signals
Protein Isoforms / genetics
Protein Isoforms / metabolism*

Substances

Nuclear Localization Signals
Protein Isoforms
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
FTO protein, human

Grants and funding

This research was supported by the MD PhD program of the Medical Faculty, University of Oslo(AA), the Research Council of Norway (AS,CB), the Norwegian Cancer Society(AS, PI) and the European Union Seventh Framework Programme (EA,AK) (FP7-PEOPLE-2013-COFUND) under grant agreement n° 609020 - Scientia Fellows. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.