title: Nucleocytoplasmic Shuttling of FTO Does Not Affect Starvation-Induced Autophagy.
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.
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Aas
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Pauline
authors.initials: P
authors.lastname: Isakson
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Christian
authors.initials: C
authors.lastname: Bindesbøll
authors.affiliation: Department of Molecular Microbiology A3.3021, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, Oslo, Norway.
authors.forename: Endalkachew A
authors.initials: EA
authors.lastname: Alemu
authors.affiliation: Department of Molecular Microbiology A3.3021, Oslo University Hospital, Rikshospitalet, Sognsvannsveien 20, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Anne
authors.identifier: http://orcid.org/0000-0003-4711-7057
authors.initials: A
authors.lastname: Simonsen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D019913:Nuclear Localization Signals; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human