{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:11:12Z","timestamp":1777543872706,"version":"3.51.4"},"reference-count":86,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T00:00:00Z","timestamp":1473984000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T00:00:00Z","timestamp":1473984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic stress and prolonged activation of defence pathways have deleterious consequences for the cell. Dietary restriction is believed to be beneficial as it induces the cellular stress response machinery. We report here that although the phenomenon is beneficial in a wild-type cell, dietary restriction leads to an inconsistent response in a cell that is already under proteotoxicity-induced stress. Using a yeast model of Huntington\u2019s disease, we show that contrary to expectation, aggregation of mutant huntingtin is exacerbated and activation of the unfolded protein response pathway is dampened under dietary restriction. Global proteomic analysis shows that when exposed to a single stress, either protein aggregation or dietary restriction, the expression of foldases like peptidyl-prolyl isomerase, is strongly upregulated. However, under combinatorial stress, this lead is lost, which results in enhanced protein aggregation and reduced cell survival. Successful designing of aggregation-targeted therapeutics will need to take additional stressors into account.<\/jats:p>","DOI":"10.1038\/srep33433","type":"journal-article","created":{"date-parts":[[2016,9,16]],"date-time":"2016-09-16T09:47:42Z","timestamp":1474019262000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Protein aggregation activates erratic stress response in dietary restricted yeast cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Ankan Kumar","family":"Bhadra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eshita","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ipsita","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,9,16]]},"reference":[{"key":"BFsrep33433_CR1","doi-asserted-by":"crossref","unstructured":"The Huntington\u2019s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosome. Cell 72, 971\u2013983 (1993).","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"BFsrep33433_CR2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature01301","volume":"421","author":"I S\u00e1nchez","year":"2003","unstructured":"S\u00e1nchez, I., Mahlke, C. & Yuan, J. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature 421, 373\u2013379 (2003).","journal-title":"Nature"},{"key":"BFsrep33433_CR3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nature02998","volume":"431","author":"M Arrasate","year":"2004","unstructured":"Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R. & Finkbeiner, S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805\u2013810 (2004).","journal-title":"Nature"},{"key":"BFsrep33433_CR4","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nsmb1215","volume":"14","author":"Y Nagai","year":"2007","unstructured":"Nagai, Y. et al. A toxic monomeric conformer of the polyglutamine protein. Nat. Struct. Mol. Biol. 14, 332\u2013340 (2007).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFsrep33433_CR5","doi-asserted-by":"crossref","first-page":"17616","DOI":"10.1073\/pnas.0408134101","volume":"101","author":"DW Colby","year":"2004","unstructured":"Colby, D. W. et al. Potent inhibition of huntingtin aggregation and cytotoxicity by a disulfide bond-free single-domain intracellular antibody. Proc. Natl. Acad. Sci. USA 101, 17616\u201317621 (2004).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep33433_CR6","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1126\/science.1141448","volume":"319","author":"WE Balch","year":"2008","unstructured":"Balch, W. E., Morimoto, R. I., Dillin, A. & Kelly, J. W. Adapting proteostasis for disease intervention. Science 319, 916\u2013919 (2008).","journal-title":"Science"},{"key":"BFsrep33433_CR7","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.cbpa.2013.04.009","volume":"17","author":"LM Ryno","year":"2013","unstructured":"Ryno, L. M., Wiseman, R. L. & Kelly, J. W. Targeting unfolded protein response signaling pathways to ameliorate protein misfolding diseases. Curr. Opin. Chem. Biol. 17, 346\u2013352 (2013).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"BFsrep33433_CR8","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrn3689","volume":"15","author":"C Hetz","year":"2014","unstructured":"Hetz, C. & Mollereau, B. Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nat. Rev. Neurosci. 15, 233\u2013249 (2014).","journal-title":"Nat. Rev. Neurosci."},{"key":"BFsrep33433_CR9","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.tcb.2014.05.003","volume":"24","author":"MS Hipp","year":"2014","unstructured":"Hipp, M. S., Park, S. H. & Hartl, F. U. Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol. 24, 506\u2013514 (2014).","journal-title":"Trends Cell Biol"},{"key":"BFsrep33433_CR10","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1093\/gerona\/glu049","volume":"69","author":"RI Morimoto","year":"2014","unstructured":"Morimoto, R. I. & Cuervo, A. M. Proteostasis and the aging proteome in health and disease. J. Gerontol. A Biol. Sci. Med. Sci. 69 Suppl 1, S33\u2013S38 (2014).","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"BFsrep33433_CR11","doi-asserted-by":"crossref","first-page":"e1001998","DOI":"10.1371\/journal.pbio.1001998","volume":"12","author":"DM Roth","year":"2014","unstructured":"Roth, D. M. et al. Modulation of the maladaptive stress response to manage diseases of protein folding. Plos Biol. 12, e1001998 (2014).","journal-title":"Plos Biol"},{"key":"BFsrep33433_CR12","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.celrep.2014.09.042","volume":"3","author":"M Brehme","year":"2014","unstructured":"Brehme, M. et al. A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep. 3, 1135\u20131150 (2014).","journal-title":"Cell Rep"},{"key":"BFsrep33433_CR13","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1038\/ncb1478","volume":"8","author":"A Kitamura","year":"2006","unstructured":"Kitamura, A. et al. Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat. Cell Biol. 8, 1163\u20131170 (2006).","journal-title":"Nat. Cell Biol."},{"key":"BFsrep33433_CR14","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/ncb1477","volume":"8","author":"S Tam","year":"2006","unstructured":"Tam, S., Geller, R., Spiess, C. & Frydman, J. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Nat. Cell Biol. 8, 1155\u20131162 (2006).","journal-title":"Nat. Cell Biol."},{"key":"BFsrep33433_CR15","doi-asserted-by":"crossref","unstructured":"Bhadra, A. K. & Roy, I. Gpd1 regulates the activity of Tcp-1 and heat shock response in yeast cells: effect on aggregation of mutant huntingtin. Mol. Neurobiol., doi: 10.1007\/s12035-015-9329-5 (2015).","DOI":"10.1007\/s12035-015-9329-5"},{"key":"BFsrep33433_CR16","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1126\/science.1124514","volume":"311","author":"T Gidalevitz","year":"2006","unstructured":"Gidalevitz, T., Ben-Zvi, A., Ho, K. H., Brignull, H. R. & Morimoto, R. I. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311, 1471\u20131474 (2006).","journal-title":"Science"},{"key":"BFsrep33433_CR17","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1126\/science.1146361","volume":"318","author":"JH Lin","year":"2007","unstructured":"Lin, J. H. et al. IRE1 signaling affects cell fate during the unfolded protein response. Science 318, 944\u2013949 (2007).","journal-title":"Science"},{"key":"BFsrep33433_CR18","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","volume":"334","author":"P Walter","year":"2011","unstructured":"Walter, P. & Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081\u20131086 (2011).","journal-title":"Science"},{"key":"BFsrep33433_CR19","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1083\/jcb.201503107","volume":"209","author":"LT Lamech","year":"2015","unstructured":"Lamech, L. T. & Haynes, C. M. The unpredictability of prolonged activation of stress response pathways. J. Cell Biol. 209, 781\u2013787 (2015).","journal-title":"J. Cell Biol."},{"key":"BFsrep33433_CR20","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.bbrc.2015.01.021","volume":"457","author":"E Weindling","year":"2015","unstructured":"Weindling, E. & Bar-Nun, S. Sir2 links the unfolded protein response and the heat shock response in a stress response network. Biochem. Biophys. Res. Commun. 457, 473\u2013478 (2015).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFsrep33433_CR21","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1093\/hmg\/dds040","volume":"21","author":"RL Vidal","year":"2012","unstructured":"Vidal, R. L. et al. Targeting the UPR transcription factor XBP1 protects against Huntington\u2019s disease through the regulation of FoxO1 and autophagy. Hum. Mol. Genet. 21, 2245\u20132262 (2012).","journal-title":"Hum. Mol. Genet."},{"key":"BFsrep33433_CR22","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1126\/science.312.5771.195d","volume":"312","author":"DA Sinclair","year":"2006","unstructured":"Sinclair, D. A., Lin, S. J. & Guarente, L. Life-span extension in yeast. Science 312, 195\u2013197 (2006).","journal-title":"Science"},{"key":"BFsrep33433_CR23","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s00018-007-6470-y","volume":"64","author":"BK Kennedy","year":"2007","unstructured":"Kennedy, B. K., Steffen, K. K. & Kaeberlein, M. Ruminations on dietary restriction and aging. Cell Mol. Life Sci. 64, 1323\u20131328 (2007).","journal-title":"Cell Mol. Life Sci."},{"key":"BFsrep33433_CR24","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1038\/ncomms4557","volume":"5","author":"RJ Colman","year":"2014","unstructured":"Colman, R. J., Beasley, T. M., Kemnitz, J. W., Johnson, S. C., Weindruch, R. & Anderson, R. M. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat. Commun. 5, 3557 (2014).","journal-title":"Nat. Commun."},{"key":"BFsrep33433_CR25","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0006-8993(99)01827-2","volume":"842","author":"H Zhu","year":"1999","unstructured":"Zhu, H., Guo, Q. & Mattson, M. P. Dietary restriction protects hippocampal neurons against the death-promoting action of a presenilin-1 mutation. Brain Res. 842, 224\u2013229 (1999).","journal-title":"Brain Res"},{"key":"BFsrep33433_CR26","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/(SICI)1097-4547(19990715)57:2<195::AID-JNR5>3.0.CO;2-P","volume":"57","author":"W Duan","year":"1999","unstructured":"Duan, W. & Mattson, M. P. Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson\u2019s disease. J. Neurosci. Res. 57, 195\u2013206 (1999).","journal-title":"J. Neurosci. Res."},{"key":"BFsrep33433_CR27","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/nature01578","volume":"423","author":"RM Anderson","year":"2003","unstructured":"Anderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O. & Sinclair, D. A. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 423, 181\u2013185 (2003).","journal-title":"Nature"},{"key":"BFsrep33433_CR28","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1016\/j.febslet.2012.07.038","volume":"586","author":"J Schleit","year":"2012","unstructured":"Schleit, J., Wasko, B. M. & Kaeberlein, M. Yeast as a model to understand the interaction between genotype and the response to calorie restriction. FEBS Lett. 586, 2868\u20132873 (2012).","journal-title":"FEBS Lett."},{"key":"BFsrep33433_CR29","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/acel.12338","volume":"14","author":"VD Longo","year":"2015","unstructured":"Longo, V. D. et al. Interventions to slow aging in humans: Are we ready? Aging Cell 14, 497\u2013510 (2015).","journal-title":"Aging Cell"},{"key":"BFsrep33433_CR30","doi-asserted-by":"crossref","first-page":"a004440","DOI":"10.1101\/cshperspect.a004440","volume":"3","author":"RC Taylor","year":"2011","unstructured":"Taylor, R. C. & Dillin, A. Aging as an event of proteostasis collapse. Cold Spring Harb. Perspect. Biol. 3, a004440 (2011).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"BFsrep33433_CR31","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1083\/jcb.200112104","volume":"157","author":"AB Meriin","year":"2002","unstructured":"Meriin, A. B. et al. Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1. J. Cell Biol. 157, 997\u20131004 (2002).","journal-title":"J. Cell Biol."},{"key":"BFsrep33433_CR32","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1021\/cn400171d","volume":"5","author":"AA Saleh","year":"2014","unstructured":"Saleh, A. A., Bhadra, A. K. & Roy, I. Cytotoxicity of mutant huntingtin fragment in yeast can be modulated by the expression level of wild type huntingtin fragment. ACS Chem. Neurosci. 5, 205\u2013215 (2014).","journal-title":"ACS Chem. Neurosci."},{"key":"BFsrep33433_CR33","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.freeradbiomed.2008.05.014","volume":"45","author":"MA Sorolla","year":"2008","unstructured":"Sorolla, M. A. et al. Proteomic and oxidative stress analysis in human brain samples of Huntington disease. Free Radic. Biol. Med. 45, 667\u2013678 (2008).","journal-title":"Free Radic. Biol. Med."},{"key":"BFsrep33433_CR34","doi-asserted-by":"crossref","first-page":"44512","DOI":"10.1074\/jbc.M111.307587","volume":"286","author":"S Hands","year":"2011","unstructured":"Hands, S., Sajjad, M. U., Newton, M. J. & Wyttenbach, A. In vitro and in vivo aggregation of a fragment of huntingtin protein directly causes free radical production. J. Biol. Chem. 286, 44512\u201344520 (2011).","journal-title":"J. Biol. Chem."},{"key":"BFsrep33433_CR35","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0140-6736(14)61010-2","volume":"384","author":"AH Schapira","year":"2014","unstructured":"Schapira, A. H., Olanow, C. W., Greenamyre, J. T. & Bezard, E. Slowing of neurodegeneration in Parkinson\u2019s disease and Huntington\u2019s disease: future therapeutic perspectives. Lancet 384, 545\u2013555 (2014).","journal-title":"Lancet"},{"key":"BFsrep33433_CR36","doi-asserted-by":"crossref","first-page":"20313","DOI":"10.1074\/jbc.272.33.20313","volume":"272","author":"BS Berlett","year":"1997","unstructured":"Berlett, B. S. & Stadtman, E. R. Protein oxidation in aging, disease, and oxidative stress. J. Biol. Chem. 272, 20313\u201320316 (1997).","journal-title":"J. Biol. Chem."},{"key":"BFsrep33433_CR37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BJ20121806","volume":"454","author":"K Singh","year":"2013","unstructured":"Singh, K., Saleh, A. A., Bhadra, A. K. & Roy, I. Hsp104 as a key modulator of prion-mediated oxidative stress in Saccharomyces cerevisiae. Biochem. J. 454, 217\u2013225 (2013).","journal-title":"Biochem. J."},{"key":"BFsrep33433_CR38","doi-asserted-by":"crossref","first-page":"e1000467","DOI":"10.1371\/journal.pgen.1000467","volume":"5","author":"M Wei","year":"2009","unstructured":"Wei, M. et al. Tor1\/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension. Plos Genet. 5, e1000467 (2009).","journal-title":"Plos Genet"},{"key":"BFsrep33433_CR39","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1016\/j.febslet.2009.10.069","volume":"583","author":"S Hohmann","year":"2009","unstructured":"Hohmann, S. Control of high osmolarity signalling in the yeast Saccharomyces cerevisiae. FEBS Lett. 583, 4025\u20134029 (2009).","journal-title":"FEBS Lett."},{"key":"BFsrep33433_CR40","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0168-9525(02)02723-3","volume":"18","author":"SM O\u2019Rourke","year":"2002","unstructured":"O\u2019Rourke, S. M., Herskowitz, I. & O\u2019Shea, E. K. Yeast go the whole HOG for the hyperosmotic response. Trends Genet. 18, 405\u2013412 (2002).","journal-title":"Trends Genet"},{"key":"BFsrep33433_CR41","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/S0306-4522(98)00400-X","volume":"89","author":"M Kim","year":"1999","unstructured":"Kim, M. et al. Forskolin and dopamine D1 receptor activation increase huntingtin\u2019s association with endosomes in immortalized neuronal cells of striatal origin. Neuroscience 89, 1159\u20131167 (1999).","journal-title":"Neuroscience"},{"key":"BFsrep33433_CR42","doi-asserted-by":"crossref","first-page":"7554","DOI":"10.1128\/MCB.23.21.7554-7565.2003","volume":"23","author":"AB Meriin","year":"2003","unstructured":"Meriin, A. B. et al. Aggregation of expanded polyglutamine domain in yeast leads to defects in endocytosis. Mol. Cell Biol. 23, 7554\u20137565 (2003).","journal-title":"Mol. Cell Biol."},{"key":"BFsrep33433_CR43","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1128\/MMBR.67.3.376-399.2003","volume":"67","author":"KJ Bitterman","year":"2003","unstructured":"Bitterman, K. J., Medvedik, O. & Sinclair, D. A. Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin. Microbiol. Mol. Biol. Rev. 67, 376\u2013399 (2003).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"BFsrep33433_CR44","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nature08981","volume":"464","author":"M Kaeberlein","year":"2010","unstructured":"Kaeberlein, M. Lessons on longevity from budding yeast. Nature 464, 513\u2013519 (2010).","journal-title":"Nature"},{"key":"BFsrep33433_CR45","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nature00829","volume":"418","author":"SJ Lin","year":"2002","unstructured":"Lin, S. J. et al. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 418, 344\u2013348 (2002).","journal-title":"Nature"},{"key":"BFsrep33433_CR46","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrm1616","volume":"6","author":"L Bordone","year":"2005","unstructured":"Bordone, L. & Guarente, L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat. Rev. Mol. Cell Biol. 6, 298\u2013305 (2005).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFsrep33433_CR47","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.exger.2013.10.001","volume":"48","author":"KM Choi","year":"2013","unstructured":"Choi, K. M., Kwon, Y. Y. & Lee, C. K. Characterization of global gene expression during assurance of lifespan extension by caloric restriction in budding yeast. Exp. Gerontol. 48, 1455\u20131468 (2013).","journal-title":"Exp. Gerontol."},{"key":"BFsrep33433_CR48","doi-asserted-by":"crossref","first-page":"29045","DOI":"10.1074\/jbc.M112.353714","volume":"287","author":"R Raynes","year":"2012","unstructured":"Raynes, R., Leckey, B. D. Jr., Nguyen, K. & Westerheide, S. D. Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans. J. Biol. Chem. 287, 29045\u201329053 (2012).","journal-title":"J. Biol. Chem."},{"key":"BFsrep33433_CR49","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1126\/science.1165946","volume":"323","author":"SD Westerheide","year":"2009","unstructured":"Westerheide, S. D., Anckar, J., Stevens, S. M. Jr., Sistonen, L. & Morimoto, R. I. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323, 1063\u20131066 (2009).","journal-title":"Science"},{"key":"BFsrep33433_CR50","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1101\/gad.1673408","volume":"22","author":"ML Duennwald","year":"2008","unstructured":"Duennwald, M. L. & Lindquist, S. Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity. Genes Dev. 22, 3308\u20133319 (2008).","journal-title":"Genes Dev"},{"key":"BFsrep33433_CR51","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s12017-013-8275-5","volume":"16","author":"RK Chaudhary","year":"2014","unstructured":"Chaudhary, R. K., Kardani, J., Singh, K., Banerjee, R. & Roy, I. Deciphering the roles of trehalose and Hsp104 in the inhibition of aggregation of mutant huntingtin in a yeast model of Huntington\u2019s disease. Neuromolecular Med. 16, 280\u2013291 (2014).","journal-title":"Neuromolecular Med"},{"key":"BFsrep33433_CR52","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/sj.cdd.4402276","volume":"15","author":"T Kudo","year":"2008","unstructured":"Kudo, T. et al. A molecular chaperone inducer protects neurons from ER stress. Cell Death Differ. 15, 364\u2013375 (2008).","journal-title":"Cell Death Differ"},{"key":"BFsrep33433_CR53","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/332462a0","volume":"332","author":"Y Kozutsumi","year":"1988","unstructured":"Kozutsumi, Y., Segal, M., Normington, K., Gething, M. J. & Sambrook, J. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332, 462\u2013464 (1988).","journal-title":"Nature"},{"key":"BFsrep33433_CR54","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/0962-8924(94)90011-6","volume":"4","author":"CE Shamu","year":"1994","unstructured":"Shamu, C. E., Cox, J. S. & Walter, P. The unfolded-protein response pathway in yeast. Trends Cell Biol. 4, 56\u201360 (1994).","journal-title":"Trends Cell Biol"},{"key":"BFsrep33433_CR55","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/ncb3184","volume":"17","author":"C Hetz","year":"2015","unstructured":"Hetz, C., Chevet, E. & Oakes, S. A. Proteostasis control by the unfolded protein response. Nat. Cell Biol. 17, 829\u2013838 (2015).","journal-title":"Nat. Cell Biol."},{"key":"BFsrep33433_CR56","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/0092-8674(93)90648-A","volume":"73","author":"JS Cox","year":"1993","unstructured":"Cox, J. S., Shamu, C. E. & Walter, P. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell 73, 1197\u20131206 (1993).","journal-title":"Cell"},{"key":"BFsrep33433_CR57","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/0092-8674(93)90521-Q","volume":"74","author":"K Mori","year":"1993","unstructured":"Mori, K., Ma, W., Gething, M. J. & Sambrook, J. A transmembrane protein with a cdc2+\/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell 74, 743\u2013756 (1993).","journal-title":"Cell"},{"key":"BFsrep33433_CR58","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/hmg\/ddr445","volume":"21","author":"H Lee","year":"2012","unstructured":"Lee, H. et al. IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux. Hum. Mol. Genet. 21, 101\u2013114 (2012).","journal-title":"Hum. Mol. Genet."},{"key":"BFsrep33433_CR59","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0092-8674(00)80835-1","volume":"101","author":"KJ Travers","year":"2000","unstructured":"Travers, K. J. et al. Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101, 249\u2013258 (2000).","journal-title":"Cell"},{"key":"BFsrep33433_CR60","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1126\/science.1092287","volume":"303","author":"GJ Steel","year":"2004","unstructured":"Steel, G. J., Fullerton, D. M., Tyson, J. R. & Stirling, C. J. Coordinated activation of Hsp70 chaperones. Science 303, 98\u2013101 (2004).","journal-title":"Science"},{"key":"BFsrep33433_CR61","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1002\/j.1460-2075.1996.tb00624.x","volume":"15","author":"RA Craven","year":"1996","unstructured":"Craven, R. A., Egerton, M. & Stirling, C. J. A novel Hsp70 of the yeast ER lumen is required for the efficient translocation of a number of protein precursors. EMBO J. 15, 2640\u20132650 (1996).","journal-title":"EMBO J."},{"key":"BFsrep33433_CR62","doi-asserted-by":"crossref","first-page":"12195","DOI":"10.1074\/jbc.M115.703256","volume":"291","author":"A Pfeiffer","year":"2016","unstructured":"Pfeiffer, A. et al. Complex of Htm1 and the oxidoreductase Pdi1 accelerates degradation of misfolded glycoproteins. J. Biol. Chem. 291, 12195\u201312207 (2016).","journal-title":"J. Biol. Chem."},{"key":"BFsrep33433_CR63","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1083\/jcb.200401157","volume":"166","author":"CD Ellis","year":"2004","unstructured":"Ellis, C. D. et al. Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function. J. Cell Biol. 166, 325\u2013335 (2004).","journal-title":"J. Cell Biol."},{"key":"BFsrep33433_CR64","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1534\/genetics.111.137760","volume":"191","author":"SW Liebman","year":"2012","unstructured":"Liebman, S. W. & Chernoff, Y. O. Prions in yeast. Genetics 191, 1041\u20131072 (2012).","journal-title":"Genetics"},{"key":"BFsrep33433_CR65","doi-asserted-by":"crossref","first-page":"e111505","DOI":"10.1371\/journal.pone.0111505","volume":"9","author":"I Nussbaum","year":"2014","unstructured":"Nussbaum, I., Weindling, E., Jubran, R., Cohen, A. & Bar-Nun, S. Deteriorated stress response in stationary-phase yeast: Sir2 and Yap1 are essential for Hsf1 activation by heat shock and oxidative stress, respectively. Plos One 9, e111505 (2014).","journal-title":"Plos One"},{"key":"BFsrep33433_CR66","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/cfg.482","volume":"6","author":"TJ Pemberton","year":"2005","unstructured":"Pemberton, T. J. & Kay, J. E. Identification and comparative analysis of the peptidyl-prolyl cis\/trans isomerase repertoires of H. sapiens, D. melanogaster, C. elegans, S. cerevisiae and Sz. pombe. Comp. Funct. Genomics 6, 277\u2013300 (2005).","journal-title":"Comp. Funct. Genomics"},{"key":"BFsrep33433_CR67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/jnc.13033","volume":"133","author":"LJ Blair","year":"2015","unstructured":"Blair, L. J., Baker, J. D., Sabbagh, J. J. & Dickey, C. A. The emerging role of peptidyl-prolyl isomerase chaperones in tau oligomerization, amyloid processing, and Alzheimer\u2019s disease. J. Neurochem. 133, 1\u201313 (2015).","journal-title":"J. Neurochem."},{"key":"BFsrep33433_CR68","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.neulet.2009.04.062","volume":"459","author":"H Sugata","year":"2009","unstructured":"Sugata, H. et al. A peptidyl-prolyl isomerase, FKBP12, accumulates in Alzheimer neurofibrillary tangles. Neurosci. Lett. 459, 96\u201399 (2009).","journal-title":"Neurosci. Lett."},{"key":"BFsrep33433_CR69","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/protein\/gzt033","volume":"26","author":"T Ikura","year":"2013","unstructured":"Ikura, T. & Ito, N. Peptidyl-prolyl isomerase activity of FK506 binding protein 12 prevents tau peptide from aggregating. Protein Eng. Des. Sel. 26, 539\u2013546 (2013).","journal-title":"Protein Eng. Des. Sel."},{"key":"BFsrep33433_CR70","doi-asserted-by":"crossref","first-page":"e1598","DOI":"10.1371\/journal.pone.0001598","volume":"3","author":"S Bandhakavi","year":"2008","unstructured":"Bandhakavi, S. et al. Hsf1 activation inhibits rapamycin resistance and TOR signaling in yeast revealed by combined proteomic and genetic analysis. Plos One 3, e1598 (2008).","journal-title":"Plos One"},{"key":"BFsrep33433_CR71","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/j.1474-9726.2012.00855.x","volume":"11","author":"A Tauffenberger","year":"2012","unstructured":"Tauffenberger, A., Vaccaro, A., Aulas, A., Vande Velde, C. & Parker, J. A. Glucose delays age-dependent proteotoxicity. Aging Cell 11, 856\u2013866 (2012).","journal-title":"Aging Cell"},{"key":"BFsrep33433_CR72","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/j.neurobiolaging.2009.10.015","volume":"32","author":"F Kerr","year":"2011","unstructured":"Kerr, F. et al. Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer\u2019s disease. Neurobiol. Aging 32, 1977\u20131989 (2011).","journal-title":"Neurobiol. Aging"},{"key":"BFsrep33433_CR73","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mcn.2015.06.001","volume":"67","author":"V Delic","year":"2015","unstructured":"Delic, V. et al. Calorie restriction does not restore brain mitochondrial function in P301L tau mice, but it does decrease mitochondrial F0F1-ATPase activity. Mol. Cell Neurosci. 67, 46\u201354 (2015).","journal-title":"Mol. Cell Neurosci."},{"key":"BFsrep33433_CR74","doi-asserted-by":"crossref","first-page":"18171","DOI":"10.1073\/pnas.0405831102","volume":"101","author":"N Maswood","year":"2004","unstructured":"Maswood, N. et al. Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson\u2019s disease. Proc. Natl. Acad. Sci. USA 101, 18171\u201318176 (2004).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFsrep33433_CR75","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.nbd.2006.12.019","volume":"26","author":"VK Halagappa","year":"2007","unstructured":"Halagappa, V. K. et al. Intermittent fasting and caloric restriction ameliorate age-related behavioural deficits in the triple-transgenic mouse model of Alzheimer\u2019s disease. Neurobiol. Dis. 26, 212\u2013220 (2007).","journal-title":"Neurobiol. Dis."},{"key":"BFsrep33433_CR76","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.nbd.2015.09.012","volume":"85","author":"CL Moreno","year":"2016","unstructured":"Moreno, C. L., Ehrlich, M. E. & Mobbs, C. V. Protection by dietary restriction in the YAC128 mouse model of Huntington\u2019s disease: Relation to genes regulating histone acetylation and HTT. Neurobiol. Dis. 85, 25\u201334 (2016).","journal-title":"Neurobiol. Dis."},{"key":"BFsrep33433_CR77","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.1210\/en.2010-0702","volume":"151","author":"MM Poplawski","year":"2010","unstructured":"Poplawski, M. M., Mastaitis, J. W., Yang, X. J. & Mobbs, C. V. Hypothalamic responses to fasting indicate metabolic reprogramming away from glycolysis toward lipid oxidation. Endocrinology 151, 5206\u20135217 (2010).","journal-title":"Endocrinology"},{"key":"BFsrep33433_CR78","doi-asserted-by":"crossref","first-page":"e9386","DOI":"10.1371\/journal.pone.0009386","volume":"5","author":"BP Patel","year":"2010","unstructured":"Patel, B. P., Safdar, A., Raha, S., Tarnopolsky, M. A. & Hamadeh, M. J. Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS. Plos One 5, e9386 (2010).","journal-title":"Plos One"},{"key":"BFsrep33433_CR79","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/acel.12362","volume":"14","author":"SC Johnson","year":"2015","unstructured":"Johnson, S. C., Dong, X., Vijg, J. & Suh, Y. Genetic evidence for common pathways in human age-related diseases. Aging Cell 14, 809\u2013817 (2015).","journal-title":"Aging Cell"},{"key":"BFsrep33433_CR80","doi-asserted-by":"crossref","first-page":"23633","DOI":"10.1074\/jbc.C113.481945","volume":"288","author":"K Bersuker","year":"2013","unstructured":"Bersuker, K., Hipp, M. S., Calamini, B., Morimoto, R. I. & Kopito, R. R. Heat shock response activation exacerbates inclusion body formation in a cellular model of Huntington disease. J. Biol. Chem. 288, 23633\u201323638 (2013).","journal-title":"J. Biol. Chem."},{"key":"BFsrep33433_CR81","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/ncb0311-184","volume":"13","author":"I Tabas","year":"2011","unstructured":"Tabas, I. & Ron, D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol. 13, 184\u2013190 (2011).","journal-title":"Nat. Cell Biol."},{"key":"BFsrep33433_CR82","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.1201396","volume":"332","author":"P Tsaytler","year":"2011","unstructured":"Tsaytler, P., Harding, H. P., Ron, D. & Bertolotti, A. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science 332, 91\u201394 (2011).","journal-title":"Science"},{"key":"BFsrep33433_CR83","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/acel.12024","volume":"12","author":"EA Morton","year":"2013","unstructured":"Morton, E. A. & Lamitina, T. Caenorhabditis elegans HSF-1 is an essential nuclear protein that forms stress granule-like structures following heat shock. Aging Cell 12, 112\u2013120 (2013).","journal-title":"Aging Cell"},{"key":"BFsrep33433_CR84","doi-asserted-by":"crossref","first-page":"5385","DOI":"10.1074\/jbc.M106846200","volume":"277","author":"CM Wong","year":"2002","unstructured":"Wong, C. M., Zhou, Y., Ng, R. W. M., Kung, H. & Jin, D. Y. Cooperation of yeast peroxiredoxins Tsa1p and Tsa2p in the cellular defense against oxidative and nitrosative stress. J. Biol. Chem. 277, 5385\u20135394 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFsrep33433_CR85","first-page":"13.12.1","volume":"23","author":"MA Collart","year":"2001","unstructured":"Collart, M. A. & Oliviero, S. Preparation of yeast RNA. Curr. Protoc. Mol. Biol. 23, 13.12.1\u201313.12.5 (2001).","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"BFsrep33433_CR86","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen, T. D. & Livak, K. J. Analyzing real-time PCR data by the comparative CT method. Nat. Protoc. 3, 1101\u20131108 (2008).","journal-title":"Nat. Protoc."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep33433.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep33433","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep33433.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:54:46Z","timestamp":1672901686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep33433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,16]]},"references-count":86,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,16]]}},"alternative-id":["BFsrep33433"],"URL":"https:\/\/doi.org\/10.1038\/srep33433","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,16]]},"assertion":[{"value":"18 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33433"}}