title: O-GlcNAc modification is essential for the regulation of autophagy in Drosophila melanogaster.
abstract: O-GlcNAcylation is a dynamic post-translational modification that takes place on ser/thr residues of nucleocytoplasmic proteins. O-GlcNAcylation regulates almost all cellular events as a nutrient sensor, a transcriptional and translational regulator, and a disease-related factor. Although the role of O-GlcNAcylation in insulin signaling and metabolism are well established, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we manipulated O-GlcNAcylation in Drosophila and found that it regulates autophagy through Akt/dFOXO signaling. We demonstrate that O-GlcNAcylation and the levels of O-GlcNAc transferase (OGT) are increased during starvation. Furthermore, Atg proteins and autolysosomes are increased in OGT-reduced flies without fasting. Atg proteins and autophagosomes are reduced in OGT-overexpressing flies. Our results suggest that not only autophagy gene expression but also autophagic structures are regulated by OGT through Akt and dFOXO. These data imply that O-GlcNAcylation is important in modulating autophagy as well as insulin signaling in Drosophila.
authors.affiliation: Department of Integrated OMICS for Biomedical Science, Graduate School, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, South Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Park
authors.forename: Yangsin
authors.initials: Y
authors.lastname: Lee
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Pak
authors.forename: Hanbyeol
authors.initials: H
authors.lastname: Kim
authors.forename: Hyeonjin
authors.initials: H
authors.lastname: Choi
authors.forename: Jae-woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Jürgen
authors.initials: J
authors.lastname: Roth
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Cho
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007328:Insulin / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011714:Pyrans; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013217:Starvation / Q000378:metabolism*; D013844:Thiazoles
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D007328:Insulin; D011714:Pyrans; D013844:Thiazoles; C572247:thiamet G; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D051057:Proto-Oncogene Proteins c-akt
references.citation: Cell Death Differ. 2007 Jun;14(6):1181-90
references.pmid: 17363962
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17669-74
references.pmid: 22988095
references.citation: Cell. 2011 May 13;145(4):596-606
references.pmid: 21565616
references.citation: J Biol Chem. 2014 May 9;289(19):13543-53
references.pmid: 24648514
references.citation: Cell. 2011 Nov 11;147(4):728-41
references.pmid: 22078875
references.citation: FEBS Lett. 2003 May 22;543(1-3):154-8
references.pmid: 12753924
references.citation: PLoS Genet. 2013 Nov;9(11):e1003941
references.pmid: 24244197
references.citation: Expert Rev Proteomics. 2013 Aug;10(4):365-80
references.pmid: 23992419
references.citation: Life Sci. 2013 Mar 28;92(11):648-56
references.pmid: 22728715
references.citation: Islets. 2009 Sep-Oct;1(2):151-3
references.pmid: 21099263
references.citation: Dev Cell. 2004 Aug;7(2):179-92
references.pmid: 15296715
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2820-5
references.pmid: 10717000
references.citation: Biochim Biophys Acta. 2004 Jul 6;1673(1-2):13-28
references.pmid: 15238246
references.citation: Trends Endocrinol Metab. 2013 Jun;24(6):301-9
references.pmid: 23647930
references.citation: J Cell Biol. 2010 Aug 23;190(4):523-31
references.pmid: 20713604
references.citation: PLoS One. 2010 Jul 09;5(7):e11521
references.pmid: 20634900
references.citation: Nat Chem Biol. 2008 Aug;4(8):483-90
references.pmid: 18587388
references.citation: Genes Dev. 2003 Aug 15;17(16):2006-20
references.pmid: 12893776
references.citation: Annu Rev Cell Dev Biol. 2011;27:107-32
references.pmid: 21801009
references.citation: J Biol Chem. 2008 Jun 13;283(24):16283-92
references.pmid: 18420577
references.citation: Cell Mol Life Sci. 2011 Oct;68(20):3377-84
references.pmid: 21365280
references.citation: Bioessays. 2001 Aug;23(8):677-82
references.pmid: 11494315
references.citation: Nat Neurosci. 2013 Oct;16(10):1453-60
references.pmid: 23995066
references.citation: Genes Dev. 2012 Mar 1;26(5):490-502
references.pmid: 22327476
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13427-32
references.pmid: 19666537
references.citation: Dev Cell. 2004 Aug;7(2):167-78
references.pmid: 15296714
references.citation: Nat Cell Biol. 2008 Apr;10(4):468-75
references.pmid: 18344986
references.citation: J Biol Chem. 2009 Oct 9;284(41):28319-31
references.pmid: 19696026
references.citation: Biochem Biophys Res Commun. 2012 Jun 1;422(2):224-8
references.pmid: 22564745
references.citation: Physiol Rev. 2010 Oct;90(4):1383-435
references.pmid: 20959619
references.citation: Am J Physiol Cell Physiol. 2010 Apr;298(4):C776-85
references.pmid: 20089931
references.citation: Nature. 2013 Oct 17;502(7471):372-6
references.pmid: 24077098