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Tim8p is located in the mitochondrial intermembrane space and forms a hetero-oligomeric complex with Tim13p to facilitate protein transport through the TIM22 translocation system. Previous research has indicated that TIM8 is not essential for yeast survival but does affect the import of Tim23p in the absence of the Tim8-Tim13 complex. Previous research on TIM8 has focused mainly on its involvement in the mitochondrial protein transport pathway, and the precise biological function of TIM8 remains incompletely understood. In this study, we provide the first report that yeast TIM8 is associated with the endoplasmic reticulum (ER) stress response and chronological senescence. We found that deletion of TIM8 leads to both oxidative stress and ER stress in yeast cells while increasing resistance to the ER stress inducer tunicamycin (TM), which is accompanied by an enhanced basic unfolded protein response (UPR). More importantly, TIM8 deficiency can lead to a shortened chronological lifespan (CLS) but does not affect the replicative lifespan (RLS). Moreover, we found that improving the antioxidant capacity further increased TM resistance in the tim8\u0394 strain. Importantly, we provide evidence that the knockdown of TIMM8A in ARPE-19 human retinal pigment epithelium cells can also induce ER stress, suggesting the potential function of the TIM8 gene in ER stress is conserved from budding yeast to higher eukaryotes. In summary, these results suggest novel roles for TIM8 in maintaining ER homeostasis and CLS maintenance.<\/jats:p>","DOI":"10.3390\/biom15020271","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T06:06:06Z","timestamp":1739340366000},"page":"271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TIM8 Deficiency in Yeast Induces Endoplasmic Reticulum Stress and Shortens the Chronological Lifespan"],"prefix":"10.3390","volume":"15","author":[{"given":"Dong","family":"Tang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbin","family":"Guan","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodi","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongqin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medical Technology, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinguang","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Medical Immunology and Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9578","DOI":"10.1073\/pnas.0914387107","article-title":"Substrate specificity of the TIM22 mitochondrial import pathway revealed with small molecule inhibitor of protein translocation","volume":"107","author":"Hasson","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23287","DOI":"10.1074\/jbc.M201154200","article-title":"The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1.TIM13 complexes in the mitochondrial intermembrane space","volume":"277","author":"Hofmann","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.1093\/emboj\/19.23.6392","article-title":"The role of the TIM8-13 complex in the import of Tim23 into mitochondria","volume":"19","author":"Paschen","year":"2000","journal-title":"EMBO J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1073\/pnas.96.5.2141","article-title":"Human deafness dystonia syndrome is a mitochondrial disease","volume":"96","author":"Koehler","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e00204-18","DOI":"10.1128\/mSphere.00204-18","article-title":"Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei","volume":"3","author":"Smith","year":"2018","journal-title":"mSphere"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e48828","DOI":"10.7554\/eLife.48828","article-title":"Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjaerg syndrome","volume":"8","author":"Kang","year":"2019","journal-title":"Elife"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.molcel.2017.06.017","article-title":"The Unfolded Protein Response and Cell Fate Control","volume":"69","author":"Hetz","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"Hetz","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lee, J.H., and Lee, J. (2022). Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic beta-Cell Dysfunction and Senescence in Type 2 Diabetes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094843"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Brown, M.K., and Naidoo, N. (2012). The endoplasmic reticulum stress response in aging and age-related diseases. Front. Physiol., 3.","DOI":"10.3389\/fphys.2012.00263"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.biochi.2023.10.019","article-title":"Crosstalk between protein misfolding and endoplasmic reticulum stress during ageing and their role in age-related disorders","volume":"221","author":"Hemagirri","year":"2024","journal-title":"Biochimie"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1093\/nar\/21.14.3329","article-title":"A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae","volume":"21","author":"Baudin","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.mad.2017.03.008","article-title":"CTT1 overexpression increases the replicative lifespan of MMS-sensitive Saccharomyces cerevisiae deficient in KSP1","volume":"164","author":"Zhao","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"foab020","DOI":"10.1093\/femsyr\/foab020","article-title":"Sterol uptake analysis in Saccharomyces and non-Saccharomyces wine yeast species","volume":"21","author":"Tesniere","year":"2021","journal-title":"FEMS Yeast Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cui, H.J., Cui, X.G., Jing, X., Yuan, Y., Chen, Y.Q., Sun, Y.X., Zhao, W., and Liu, X.G. (2019). GAS1 Deficient Enhances UPR Activity in Saccharomyces cerevisiae. Biomed. Res. Int., 2019.","DOI":"10.1155\/2019\/1238581"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Olsen, B., Murakami, C.J., and Kaeberlein, M. (2010). YODA: Software to facilitate high-throughput analysis of chronological life span, growth rate, and survival in budding yeast. BMC Bioinformatics, 11.","DOI":"10.1186\/1471-2105-11-141"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ijfoodmicro.2007.03.005","article-title":"Modelling of the growth-no growth interface of Issatchenkia occidentalis, an olive spoiling yeast, as a function of the culture media, NaCl, citric and sorbic acid concentrations: Study of its inactivation in the no growth region","volume":"117","author":"Quintana","year":"2007","journal-title":"Int. J. Food Microbiol."},{"key":"ref_18","first-page":"58192","article-title":"Saccharomyces cerevisiae exponential growth kinetics in batch culture to analyze respiratory and fermentative metabolism","volume":"139","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"foy057","DOI":"10.1093\/femsyr\/foy057","article-title":"ERG11 couples oxidative stress adaptation, hyphal elongation and virulence in Candida albicans","volume":"18","author":"Wu","year":"2018","journal-title":"FEMS Yeast Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4517091","DOI":"10.1155\/2019\/4517091","article-title":"Cucurbitacin B Exerts Antiaging Effects in Yeast by Regulating Autophagy and Oxidative Stress","volume":"2019","author":"Lin","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1091\/mbc.E18-06-0356","article-title":"Reciprocal interactions between mtDNA and lifespan control in budding yeast","volume":"30","author":"Garcia","year":"2019","journal-title":"Mol. Biol. Cell"},{"key":"ref_22","first-page":"32","article-title":"Simulated microgravity accelerates aging in Saccharomyces cerevisiae","volume":"28","author":"Fukuda","year":"2021","journal-title":"Life Sci. Space Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.18632\/aging.101350","article-title":"Mitogen-activated protein kinases, Fus3 and Kss1, regulate chronological lifespan in yeast","volume":"9","author":"Aluru","year":"2017","journal-title":"Aging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111480","DOI":"10.1016\/j.mad.2021.111480","article-title":"The Spt7 subunit of the SAGA complex is required for the regulation of lifespan in both dividing and nondividing yeast cells","volume":"196","author":"Lim","year":"2021","journal-title":"Mech. Ageing Dev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e0076521","DOI":"10.1128\/msphere.00765-21","article-title":"Tup1 Paralog CgTUP11 Is a Stronger Repressor of Transcription than CgTUP1 in Candida glabrata","volume":"7","author":"Bui","year":"2022","journal-title":"mSphere"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"fox015","DOI":"10.1093\/femsyr\/fox015","article-title":"Transcription factor Mxr1 promotes the expression of Aox1 by repressing glycerol transporter 1 in Pichia pastoris","volume":"17","author":"Zhan","year":"2017","journal-title":"FEMS Yeast Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Labunskyy, V.M., Gerashchenko, M.V., Delaney, J.R., Kaya, A., Kennedy, B.K., Kaeberlein, M., and Gladyshev, V.N. (2014). Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004019"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1074\/jbc.M708597200","article-title":"Complex I is the major site of mitochondrial superoxide production by paraquat","volume":"283","author":"Cocheme","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113998","DOI":"10.1016\/j.fct.2023.113998","article-title":"GRPR down-regulation inhibits spermatogenesis through Ca2+ mediated by PLCbeta\/IP3R signaling pathway in long-term formaldehyde-exposed rats","volume":"179","author":"Yang","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Selvaraj, B., Le, T.T., Kim, D.W., Jung, B.H., Yoo, K.Y., Ahn, H.R., Thuong, P.T., Tran, T.T.T., Pae, A.N., and Jung, S.H. (2023). Neuroprotective Effects of Ethanol Extract of Polyscias fruticosa (EEPF) against Glutamate-Mediated Neuronal Toxicity in HT22 Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043969"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Zhang, L., Zhou, L., Lei, Y., Zhang, Y., and Huang, C. (2019). Redox signaling and unfolded protein response coordinate cell fate decisions under ER stress. Redox Biol., 25.","DOI":"10.1016\/j.redox.2018.11.005"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1091\/mbc.8.10.1845","article-title":"Endoplasmic reticulum stress-induced mRNA splicing permits synthesis of transcription factor Hac1p\/Ern4p that activates the unfolded protein response","volume":"8","author":"Kawahara","year":"1997","journal-title":"Mol. Biol. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.exger.2012.12.001","article-title":"Dietary restriction and mitochondrial function link replicative and chronological aging in Saccharomyces cerevisiae","volume":"48","author":"Delaney","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/ng1096-177","article-title":"A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness","volume":"14","author":"Jin","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.celrep.2014.09.016","article-title":"Ire1 has distinct catalytic mechanisms for XBP1\/HAC1 splicing and RIDD","volume":"9","author":"Tam","year":"2014","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wu, H., Ng, B.S., and Thibault, G. (2014). Endoplasmic reticulum stress response in yeast and humans. Biosci. Rep., 34.","DOI":"10.1042\/BSR20140058"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.arr.2010.04.003","article-title":"ER stress and hormetic regulation of the aging process","volume":"9","author":"Salminen","year":"2010","journal-title":"Ageing Res. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3390\/ijms14010434","article-title":"An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases","volume":"14","author":"Bhandary","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.cellsig.2016.05.007","article-title":"Bridges between mitochondrial oxidative stress, ER stress and mTOR signaling in pancreatic beta cells","volume":"28","author":"Wang","year":"2016","journal-title":"Cell Signal"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s40292-023-00611-3","article-title":"Beyond Glucose: The Dual Assault of Oxidative and ER Stress in Diabetic Disorders","volume":"30","author":"Roohi","year":"2023","journal-title":"High. Blood Press. Cardiovasc. Prev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mizuno, T., Nakamura, M., and Irie, K. (2018). Induction of Ptp2 and Cmp2 protein phosphatases is crucial for the adaptive response to ER stress in Saccharomyces cerevisiae. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31413-6"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Osman, A., El-Gamal, H., Pasha, M., Zeidan, A., Korashy, H.M., Abdelsalam, S.S., Hasan, M., Benameur, T., and Agouni, A. (2020). Endoplasmic Reticulum (ER) Stress-Generated Extracellular Vesicles (Microparticles) Self-Perpetuate ER Stress and Mediate Endothelial Cell Dysfunction Independently of Cell Survival. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.584791"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kapitzky, L., Beltrao, P., Berens, T.J., Gassner, N., Zhou, C., W\u00fcster, A., Wu, J., Babu, M.M., Elledge, S.J., and Toczyski, D. (2010). Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action. Mol. Syst. Biol., 6.","DOI":"10.1038\/msb.2010.107"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10605","DOI":"10.1073\/pnas.152264899","article-title":"Previously uncharacterized genes in the UV-and MMS-induced DNA damage response in yeast","volume":"99","author":"Hanway","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.freeradbiomed.2008.07.018","article-title":"DNA damage-induced reactive oxygen species (ROS) stress response in Saccharomyces cerevisiae","volume":"45","author":"Rowe","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3565127","DOI":"10.1155\/2016\/3565127","article-title":"ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases","volume":"2016","author":"Davalli","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"Finkel","year":"2000","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00284-017-1412-x","article-title":"Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and Apoptotic Stress and Extends Chronological Lifespan","volume":"75","author":"Alugoju","year":"2018","journal-title":"Curr. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.4161\/cc.22041","article-title":"Chronological and replicative lifespan in yeast: Do they meet in the middle?","volume":"11","author":"Polymenis","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.febslet.2008.11.028","article-title":"Mitochondrial dysfunction leads to reduced chronological lifespan and increased apoptosis in yeast","volume":"583","author":"Aerts","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cmet.2012.05.013","article-title":"Mitochondrial Respiratory Thresholds Regulate Yeast Chronological Life Span and its Extension by Caloric Restriction","volume":"16","author":"Ocampo","year":"2012","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.4161\/cc.8.8.8287","article-title":"A molecular mechanism of chronological aging in yeast","volume":"8","author":"Burtner","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nature08981","article-title":"Lessons on longevity from budding yeast","volume":"464","author":"Kaeberlein","year":"2013","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gast, V., Campbell, K., Picazo, C., Engqvist, M., Siewers, V., and Molin, M. (2021). The Yeast eIF2 Kinase Gcn2 Facilitates H2O2-Mediated Feedback Inhibition of Both Protein Synthesis and Endoplasmic Reticulum Oxidative Folding during Recombinant Protein Production. Appl. Environ. Microbiol., 87.","DOI":"10.1128\/AEM.00301-21"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"An, M.Y., Lee, S.R., Hwang, H.J., Yoon, J.G., Lee, H.J., and Cho, J.A. (2021). Antioxidant and Anti-Inflammatory Effects of Korean Black Ginseng Extract through ER Stress Pathway. Antioxidants, 10.","DOI":"10.3390\/antiox10010062"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1379\/CSC-103R.1","article-title":"The role of cytoplasmic catalase in dehydration tolerance of Saccharomyces cerevisiae","volume":"10","author":"Franca","year":"2005","journal-title":"Cell Stress. Chaperones"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: From stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Afsar, E., Kirimlioglu, E., Ceker, T., Yilmaz, C., Demir, N., and Aslan, M. (2020). Effect of ER stress on sphingolipid levels and apoptotic pathways in retinal pigment epithelial cells. Redox Biol., 30.","DOI":"10.1016\/j.redox.2020.101430"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.humpath.2018.08.009","article-title":"Expressions of ATF6, XBP1, and GRP78 in normal tissue, atypical adenomatous hyperplasia, and adenocarcinoma of the lung","volume":"83","author":"Ogata","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Aghaei, M., Nasimian, A., Rahmati, M., Kawalec, P., Machaj, F., Rosik, J., Bhushan, B., Bathaie, S.Z., Azarpira, N., and Los, M.J. (2021). The Role of BiP and the IRE1alpha-XBP1 Axis in Rhabdomyosarcoma Pathology. Cancers, 13.","DOI":"10.3390\/cancers13194927"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102961","DOI":"10.1016\/j.ceca.2024.102961","article-title":"ER stress as a sentinel mechanism for ER Ca2+ homeostasis","volume":"124","author":"Makio","year":"2024","journal-title":"Cell Calcium"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.bbrc.2015.02.004","article-title":"Ca2+ homeostasis and endoplasmic reticulum (ER) stress: An integrated view of calcium signaling","volume":"460","author":"Krebs","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ircmb.2021.03.003","article-title":"Calcium signaling and endoplasmic reticulum stress","volume":"363","author":"Groenendyk","year":"2021","journal-title":"Int. Rev. Cell Mol. 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