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Research Paper

The unfolded protein response regulates hepatic autophagy by sXBP1-mediated activation of TFEB

ORCID Icon, , , , , ORCID Icon, , , , ORCID Icon & ORCID Icon show all
Pages 1841-1855 | Received 09 Sep 2019, Accepted 10 Jun 2020, Published online: 15 Jul 2020

References

  • Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007 Jul;8(7):519–529.
  • Sidrauski C, Walter P. The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell. 1997 Sep 19;90(6):1031–1039.
  • Lee AH, Iwakoshi NN, Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol. 2003 Nov;23(21):7448–7459.
  • Lee AH, Scapa EF, Cohen DE, et al. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science. 2008 Jun 13;320(5882):1492–1496.
  • Park SW, Zhou Y, Lee J, et al. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nat Med. 2010 Apr;16(4):429–437.
  • Zhou Y, Lee J, Reno CM, et al. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nat Med. 2011 Mar;17(3):356–365.
  • Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004 Oct 15;306(5695):457–461.
  • Zhang K, Wang S, Malhotra J, et al. The unfolded protein response transducer IRE1alpha prevents ER stress-induced hepatic steatosis. Embo J. 2011 Apr 6;30(7):1357–1375.
  • Zeng L, Zampetaki A, Margariti A, et al. Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8326–8331.
  • Puri P, Mirshahi F, Cheung O, et al. Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease. Gastroenterology. 2008 Feb;134(2):568–576.
  • Wang JM, Qiu Y, Yang Z, et al. IRE1alpha prevents hepatic steatosis by processing and promoting the degradation of select microRNAs. Sci Signal. 2018 May 15;11(530):eaao4617.
  • Kim RS, Hasegawa D, Goossens N, et al. The XBP1 arm of the unfolded protein response induces fibrogenic activity in hepatic stellate cells through autophagy. Sci Rep. 2016 Dec 20;6(1):39342.
  • Ozcan U, Yilmaz E, Ozcan L, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006 Aug 25;313(5790):1137–1140.
  • Kars M, Yang L, Gregor MF, et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 2010 Aug;59(8):1899–1905.
  • Ohsumi Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol. 2001 Mar;2(3):211–216.
  • Koyano F, Okatsu K, Kosako H, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014 Jun 05;510(7503):162–166.
  • Iwata J, Ezaki J, Komatsu M, et al. Excess peroxisomes are degraded by autophagic machinery in mammals. J Biol Chem. 2006 Feb 17;281(7):4035–4041.
  • Tripathi DN, Walker CL. The peroxisome as a cell signaling organelle. Curr Opin Cell Biol. 2016 Apr;39:109–112.
  • Singh R, Kaushik S, Wang Y, et al. Autophagy regulates lipid metabolism. Nature. 2009 Apr 30;458(7242):1131–1135.
  • Bernales S, Schuck S, Walter P. ER-phagy: selective autophagy of the endoplasmic reticulum. Autophagy. 2007 May-Jun;3(3):285–287.
  • Schneider JL, Cuervo AM. Liver autophagy: much more than just taking out the trash. Nat Rev Gastroenterol Hepatol. 2014 Mar;11(3):187–200.
  • Ueno T, Komatsu M. Autophagy in the liver: functions in health and disease. Nat Rev Gastroenterol Hepatol. 2017 Mar;14(3):170–184.
  • Settembre C, Di Malta C, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011 Jun 17;332(6036):1429–1433.
  • Kaushik S, Rodriguez-Navarro JA, Arias E, et al. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance. Cell Metab. 2011 Aug 3;14(2):173–183.
  • Yang L, Li P, Fu S, et al. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance [research support, N.I.H., extramural research support, non-U.S. gov’t]. Cell Metab. 2010 Jun 9;11(6):467–478.
  • Ebato C, Uchida T, Arakawa M, et al. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab. 2008 Oct;8(4):325–332.
  • Jung HS, Chung KW, Won Kim J, et al. Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab. 2008 Oct;8(4):318–324.
  • Masiero E, Agatea L, Mammucari C, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009 Dec;10(6):507–515.
  • Arai C, Miyake M, Matsumoto Y, et al. Trehalose prevents adipocyte hypertrophy and mitigates insulin resistance in mice with established obesity. J Nutr Sci Vitaminol (Tokyo). 2013;59(5):393–401.
  • Allaire M, Rautou PE, Codogno P, et al. Autophagy in liver diseases: time for translation? J Hepatol. 2019 May;70(5):985–998.
  • Hayashi-Nishino M, Fujita N, Noda T, et al. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol. 2009 Dec;11(12):1433–1437.
  • Tooze SA, Yoshimori T. The origin of the autophagosomal membrane. Nat Cell Biol. 2010 Sep;12(9):831–835.
  • B’Chir W, Maurin AC, Carraro V, et al. The eIF2alpha/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res. 2013 Sep;41(16):7683–7699.
  • Gade P, Ramachandran G, Maachani UB, et al. An IFN-gamma-stimulated ATF6-C/EBP-beta-signaling pathway critical for the expression of death associated protein kinase 1 and induction of autophagy. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10316–10321.
  • Margariti A, Li H, Chen T, et al. XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation. J Biol Chem. 2013 Jan 11;288(2):859–872.
  • Vidal RL, Figueroa A, Court FA, et al. Targeting the UPR transcription factor XBP1 protects against huntington’s disease through the regulation of FoxO1 and autophagy. Hum Mol Genet. 2012 May 15;21(10):2245–2262.
  • Zhao Y, Li X, Cai MY, et al. XBP-1u suppresses autophagy by promoting the degradation of FoxO1 in cancer cells. Cell Res. 2013 Apr;23(4):491–507.
  • Zhou Y, Zhang S, Dai C, et al. Quinocetone triggered ER stress-induced autophagy via ATF6/DAPK1-modulated mAtg9a trafficking. Cell Biol Toxicol. 2016 Apr;32(2):141–152.
  • Adolph TE, Tomczak MF, Niederreiter L, et al. Paneth cells as a site of origin for intestinal inflammation. Nature. 2013 Nov 14;503(7475):272–276.
  • Hampe J, Franke A, Rosenstiel P, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for crohn disease in ATG16L1. Nat Genet. 2007 Feb;39(2):207–211.
  • Hetz C, Thielen P, Matus S, et al. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev. 2009 Oct 1;23(19):2294–2306.
  • Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, et al. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell. 2015 Jun 18;161(7):1527–1538.
  • Ma XH, Piao SF, Dey S, et al. Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest. 2014 Mar;124(3):1406–1417.
  • Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010 Mar 19;140(6):900–917.
  • Lowell BB. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 Jan 21;307(5708):384–387.
  • Engin F, Nguyen T, Yermalovich A, et al. Aberrant islet unfolded protein response in type 2 diabetes [research support, non-U.S. gov’t]. Sci Rep. 2014;4(1):4054.
  • Gonzalez-Rodriguez A, Mayoral R, Agra N, et al. Impaired autophagic flux is associated with increased endoplasmic reticulum stress during the development of NAFLD. Cell Death Dis. 2014 Apr;17(5):e1179.
  • Kashima J, Shintani-Ishida K, Nakajima M, et al. Immunohistochemical study of the autophagy marker microtubule-associated protein 1 light chain 3 in normal and steatotic human livers. Hepatol Res. 2014 Jul;44(7):779–787.
  • Deng Y, Wang ZV, Tao C, et al. The Xbp1s/GalE axis links ER stress to postprandial hepatic metabolism [research support, N.I.H., extramural research support, non-U.S. gov’t]. J Clin Invest. 2013 Jan 2;123(1):455–468.
  • Shao M, Shan B, Liu Y, et al. Hepatic IRE1alpha regulates fasting-induced metabolic adaptive programs through the XBP1s-PPARalpha axis signalling. Nat Commun. 2014 Mar 27;5(1):3528.
  • Hetz C, Lee AH, Gonzalez-Romero D, et al. Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):757–762.
  • Wang Y, Vera L, Fischer WH, et al. The CREB coactivator CRTC2 links hepatic ER stress and fasting gluconeogenesis. Nature. 2009 Jul 23;460(7254):534–537.
  • Yang L, Calay ES, Fan J, et al. METABOLISM. S-nitrosylation links obesity-associated inflammation to endoplasmic reticulum dysfunction [research support, N.I.H., extramural research support, non-U.S. gov’t]. Science. 2015 Jul 31;349(6247):500–506.
  • Inami Y, Yamashina S, Izumi K, et al. Hepatic steatosis inhibits autophagic proteolysis via impairment of autophagosomal acidification and cathepsin expression. Biochem Biophys Res Commun. 2011 Sep 09;412(4):618–625.
  • Qian Q, Zhang Z, Orwig A, et al. S-nitrosoglutathione reductase dysfunction contributes to obesity-associated hepatic insulin resistance via regulating autophagy. Diabetes. 2018 Feb;67(2):193–207.
  • Schneider JL, Suh Y, Cuervo AM. Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation. Cell Metab. 2014 Sep 2;20(3):417–432.
  • Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, et al. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity. 2004 Jul;21(1):81–93.
  • Martina JA, Diab HI, Brady OA, et al. TFEB and TFE3 are novel components of the integrated stress response. Embo J. 2016 Mar 1;35(5):479–495.
  • Nekrutenko A, He J. Functionality of unspliced XBP1 is required to explain evolution of overlapping reading frames. Trends Genet. 2006 Dec;22(12):645–648.
  • Tirosh B, Iwakoshi NN, Glimcher LH, et al. Rapid turnover of unspliced Xbp-1 as a factor that modulates the unfolded protein response. J Biol Chem. 2006 Mar 3;281(9):5852–5860.
  • Yoshida H, Oku M, Suzuki M, et al. pXBP1(U) encoded in XBP1 pre-mRNA negatively regulates unfolded protein response activator pXBP1(S) in mammalian ER stress response. J Cell Biol. 2006 Feb 13;172(4):565–575.
  • Zhang H, Yan S, Khambu B, et al. Dynamic MTORC1-TFEB feedback signaling regulates hepatic autophagy, steatosis and liver injury in long-term nutrient oversupply. Autophagy. 2018;14(10):1779–1795.
  • Palmieri M, Impey S, Kang H, et al. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum Mol Genet. 2011 Oct 1;20(19):3852–3866.
  • Cortes CJ, Miranda HC, Frankowski H, et al. Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA. Nat Neurosci. 2014 Sep;17(9):1180–1189.
  • Kimura S, Noda T, Yoshimori T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy. 2007 Sep-Oct;3(5):452–460.
  • Settembre C, De Cegli R, Mansueto G, et al. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol. 2013 Jun;15(6):647–658.
  • Ogata M, Hino S, Saito A, et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 2006 Dec;26(24):9220–9231.
  • Qian Q, Zhang Z, Li M, et al. Hepatic lysosomal iNOS activity impairs autophagy in obesity. Cell Mol Gastroenterol Hepatol. 2019;8(1):95–110.
  • Herrema H, Zhou Y, Zhang D, et al. XBP1s is an anti-lipogenic protein. J Biol Chem. 2016 Aug 12;291(33):17394–17404.
  • Liu HY, Han J, Cao SY, et al. Hepatic autophagy is suppressed in the presence of insulin resistance and hyperinsulinemia: inhibition of FoxO1-dependent expression of key autophagy genes by insulin. J Biol Chem. 2009 Nov 6;284(45):31484–31492.
  • Kang JW, Cho HI, Lee SM. Melatonin inhibits mTOR-dependent autophagy during liver ischemia/reperfusion. Cell Physiol Biochem. 2014;33(1):23–36.
  • Koga H, Kaushik S, Cuervo AM. Altered lipid content inhibits autophagic vesicular fusion. Faseb J. 2010 Aug;24(8):3052–3065.
  • Lee JM, Wagner M, Xiao R, et al. Nutrient-sensing nuclear receptors coordinate autophagy. Nature. 2014 Dec 04;516(7529):112–115.
  • Seok S, Fu T, Choi SE, et al. Transcriptional regulation of autophagy by an FXR-CREB axis. Nature. 2014 Dec 04;516(7529):108–111.
  • Imanikia S, Ozbey NP, Krueger C, et al. Neuronal XBP-1 activates intestinal lysosomes to improve proteostasis in C. elegans. Curr Biol. 2019 Jul 22;29(14):2322–2338 e7.
  • Imanikia S, Sheng M, Castro C, et al. XBP-1 remodels lipid metabolism to extend longevity. Cell Rep. 2019 Jul 16;28(3):581–589 e4.
  • Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for illumina sequence data. Bioinformatics. 2014 Aug 1;30(15):2114–2120.
  • Patro R, Duggal G, Love MI, et al. Salmon provides fast and bias-aware quantification of transcript expression. Nat Methods. 2017 Apr;14(4):417–419.
  • Soneson C, Love MI, Robinson MD. Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Res. 2015;4:1521.
  • Gentleman RC, Carey VJ, Bates DM, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5(10):R80.
  • Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.
  • Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545–15550.
  • Kuleshov MV, Jones MR, Rouillard AD, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016 Jul 8;44(W1):W90–7.
  • Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019 Jan 8;47(D1):D607–D613.
  • Grant CE, Bailey TL, Noble WS. FIMO: scanning for occurrences of a given motif. Bioinformatics. 2011 Apr 1;27(7):1017–1018.
  • Fornes O, Castro-Mondragon JA, Khan A, et al. JASPAR 2020: update of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2020 Jan 8;48(D1):D87–D92.

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