{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:19:12Z","timestamp":1790201952104,"version":"4.1.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Type 2 diabetes (T2D) is characterized by progressive pancreatic \u03b2-cell dysfunction and loss, driven by chronic exposure to elevated circulating free fatty acids (FFAs). Mitochondria-associated endoplasmic reticulum membranes (MAMs), the specialized contact sites between the endoplasmic reticulum (ER) and mitochondria, regulate cellular metabolism and survival, yet their role in \u03b2\u2212cell lipotoxicity remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined the impact of physiologically relevant long\u2212chain saturated (palmitic and stearic acid) and unsaturated (palmitoleic and oleic acid) FFAs, applied alone or in combination, on MAM formation in insulin\u2212secreting INS\u22121E cells. ER-mitochondria contacts were quantified by proximity\u2212ligand assay (PLA), transmission electron microscopy and genetically encoded MAM sensors. The role of reactive oxygen species was investigated using the H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \u2212scavenging enzyme glutathione peroxidase 8 (GPX8). To test causality, ER\u2212mitochondria coupling was artificially enhanced with a synthetic ER\u2212mitochondrial linker.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Saturated FFAs significantly increased ER-mitochondria contacts, whereas unsaturated FFAs had no negative effect and counteracted the saturated FFA-induced MAM formation. Expression of GPx8 suppressed palmitate\u2212induced MAM formation, indicating that H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      \u2212mediated oxidative stress is required for the saturated FFA-induced MAM remodeling. Cells expressing the synthetic linker displayed heightened susceptibility to lipotoxic stress, confirming that sustained ER\u2212mitochondria coupling promotes \u03b2\u2212cell death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our data demonstrate that dysregulated MAMs constitute a mechanistic link between saturated\u2212FFA-induced lipotoxic stress and \u03b2\u2212cell failure in T2D. Targeting MAM remodeling or the upstream H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      signal may represent a novel therapeutic avenue to preserve \u03b2\u2212cell function under lipotoxic conditions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1852671","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:41:18Z","timestamp":1784785278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-chain saturated free fatty acids induce pancreatic \u03b2\u2212cell lipotoxic stress via H2O2\u2212mediated mitochondria-associated membrane remodeling"],"prefix":"10.3389","volume":"17","author":[{"given":"Sarah","family":"Sharifi","sequence":"first","affiliation":[{"name":"Institute of Clinical Biochemistry, Hannover Medical School","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike","family":"Knittel","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Hannover Medical School","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"B\u00f6ger","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Hannover Medical School","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"J\u00f6rns","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Hannover Medical School","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilir","family":"Mehmeti","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Hannover Medical School","place":["Hannover, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nrendo.2017.151","article-title":"Global aetiology and epidemiology of type 2 diabetes mellitus and its complications","volume":"14","author":"Zheng","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119","article-title":"Idf diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B3","volume-title":"Type 2 diabetes in children and adolescents- a focus on diagnosis and treatment","author":"Pinhas-Hamiel","year":"2023"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0012","article-title":"The cost of diabetes care-an elephant in the room","volume":"41","author":"Riddle","year":"2018","journal-title":"Diabetes Care"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v14.i3.130","article-title":"Pancreatic beta-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress","volume":"14","author":"Dludla","year":"2023","journal-title":"World J Diabetes"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.09.016","article-title":"Recent insights into mechanisms of beta-cell lipo- and glucolipotoxicity in type 2 diabetes","volume":"432","author":"Lytrivi","year":"2020","journal-title":"J Mol Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13703","article-title":"Mechanisms of lipotoxicity-induced dysfunction and death of human pancreatic beta cells under obesity and type 2 diabetes conditions","volume":"25","author":"Pl\u00f6tz","year":"2024","journal-title":"Obes Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2014.02.003","article-title":"Lipotoxic endoplasmic reticulum stress, beta cell failure, and type 2 diabetes mellitus","volume":"25","author":"Biden","year":"2014","journal-title":"Trends Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.07.021","article-title":"Er-resident antioxidative Gpx7 and Gpx8 enzyme isoforms protect insulin-secreting Ins-1e beta-cells against lipotoxicity by improving the ER antioxidative capacity","volume":"112","author":"Mehmeti","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202201237R","article-title":"Luminal H(2) O(2) promotes ER Ca(2+) dysregulation and toxicity of palmitate in insulin-secreting Ins-1e cells","volume":"37","author":"Sharifi","year":"2023","journal-title":"FASEB J"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103170","article-title":"Non-esterified fatty acid palmitate facilitates oxidative endoplasmic reticulum stress and apoptosis of beta-cells by upregulating Ero-1alpha expression","volume":"73","author":"Sharifi","year":"2024","journal-title":"Redox Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M009449","article-title":"Lipidomics reveals a remarkable diversity of lipids in human plasma","volume":"51","author":"Quehenberger","year":"2010","journal-title":"J Lipid Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.026062","article-title":"Initiation and execution of lipotoxic ER stress in pancreatic beta-cells","volume":"121","author":"Cunha","year":"2008","journal-title":"J Cell Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1207385","article-title":"ER tubules mark sites of mitochondrial division","volume":"334","author":"Friedman","year":"2011","journal-title":"Science"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5370.1763","article-title":"Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses","volume":"280","author":"Rizzuto","year":"1998","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","first-page":"R87","DOI":"10.1530\/JME-16-0189","article-title":"Metabolic signaling functions of ER-mitochondria contact sites: Role in metabolic diseases","volume":"58","author":"Tubbs","year":"2017","journal-title":"J Mol Endocrinol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.86608","article-title":"Broadening horizons: The contribution of mitochondria-associated endoplasmic reticulum membrane (MAM) dysfunction in diabetic kidney disease","volume":"19","author":"Liu","year":"2023","journal-title":"Int J Biol Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/s41419-022-04942-2","article-title":"Cell death regulation by MAMs: From molecular mechanisms to therapeutic implications in cardiovascular diseases","volume":"13","author":"Li","year":"2022","journal-title":"Cell Death Dis"},{"key":"B19","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1038\/s41419-018-0416-1","article-title":"The role of endoplasmic reticulum-mitochondria contact sites in the control of glucose homeostasis: An update","volume":"9","author":"Rieusset","year":"2018","journal-title":"Cell Death Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.06.029","article-title":"Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface","volume":"39","author":"Csordas","year":"2010","journal-title":"Mol Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.02.009","article-title":"Endoplasmic reticulum-mitochondrial contactology: Structure and signaling functions","volume":"28","author":"Csordas","year":"2018","journal-title":"Trends Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41580-019-0180-9","article-title":"The functional universe of membrane contact sites","volume":"21","author":"Prinz","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1007\/s00018-024-05286-0","article-title":"Redox regulation of UPR signalling and mitochondrial ER contact sites","volume":"81","author":"Casas-Martinez","year":"2024","journal-title":"Cell Mol Life Sci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/db18-1112","article-title":"Differential effect of glucose on ER-mitochondria Ca(2+) exchange participates in insulin secretion and glucotoxicity-mediated dysfunction of beta-cells","volume":"68","author":"Dingreville","year":"2019","journal-title":"Diabetes"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3735","article-title":"Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity","volume":"20","author":"Arruda","year":"2014","journal-title":"Nat Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2337\/db18-0363","article-title":"Pdk4 augments ER-mitochondria contact to dampen skeletal muscle insulin signaling during obesity","volume":"68","author":"Thoudam","year":"2019","journal-title":"Diabetes"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.06.010","article-title":"Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes","volume":"22","author":"Arruda","year":"2015","journal-title":"Cell Metab"},{"key":"B28","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1186\/s12964-024-01914-1","article-title":"Inhibition of SGLT2 protects podocytes in diabetic kidney disease by rebalancing mitochondria-associated endoplasmic reticulum membranes","volume":"22","author":"Li","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2022.12.003","article-title":"Ferulic acid attenuates high glucose-induced MAM alterations via PACS2\/IP3R2\/FUNDC1\/VDAC1 pathway activating proapoptotic proteins and ameliorates cardiomyopathy in diabetic rats","volume":"372","author":"Salin Raj","year":"2023","journal-title":"Int J Cardiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1038\/s41467-023-37214-4","article-title":"Enhanced Ca(2+)-channeling complex formation at the ER-mitochondria interface underlies the pathogenesis of alcohol-associated liver disease","volume":"14","author":"Thoudam","year":"2023","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0316","article-title":"Disruption of mitochondria-associated endoplasmic reticulum membrane (MAM) integrity contributes to muscle insulin resistance in mice and humans","volume":"67","author":"Tubbs","year":"2018","journal-title":"Diabetes"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1751","article-title":"Mitochondria-associated endoplasmic reticulum membrane (MAM) integrity is required for insulin signaling and is implicated in hepatic insulin resistance","volume":"63","author":"Tubbs","year":"2014","journal-title":"Diabetes"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2023.0275","article-title":"Pdzd8 augments endoplasmic reticulum-mitochondria contact and regulates Ca2+ dynamics and CypD expression to induce pancreatic beta-cell death during diabetes","volume":"48","author":"Liu","year":"2024","journal-title":"Diabetes Metab J"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101368","article-title":"Grp75 mediates endoplasmic reticulum-mitochondria coupling during palmitate-induced pancreatic beta-cell apoptosis","volume":"297","author":"Tiwary","year":"2021","journal-title":"J Biol Chem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/endo.130.1.1370150","article-title":"Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines","volume":"130","author":"Asfari","year":"1992","journal-title":"Endocrinology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.2144\/000114285","article-title":"In vitro use of free fatty acids bound to albumin: A comparison of protocols","volume":"58","author":"Oliveira","year":"2015","journal-title":"Biotechniques"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101554","article-title":"In situ detection of protein-protein interaction by proximity ligation assay in patient derived brain tumor stem cells","volume":"3","author":"Sharanek","year":"2022","journal-title":"STAR Protoc"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.08.010","article-title":"The H2O2-sensitive Hyper protein targeted to the endoplasmic reticulum as a mirror of the oxidizing thiol-disulfide milieu","volume":"53","author":"Mehmeti","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.72.12.9873-9880.1998","article-title":"Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery","volume":"72","author":"Zufferey","year":"1998","journal-title":"J Virol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1159\/000430261","article-title":"Antagonism between saturated and unsaturated fatty acids in ROS mediated lipotoxicity in rat insulin-producing cells","volume":"36","author":"Gehrmann","year":"2015","journal-title":"Cell Physiol Biochem"},{"key":"B41","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41420-024-01918-3","article-title":"Mitochondria-associated endoplasmic reticulum membrane (MAM): A dark horse for diabetic cardiomyopathy treatment","volume":"10","author":"Liu","year":"2024","journal-title":"Cell Death Discov"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.03.017","article-title":"Endoplasmic reticulum-mitochondria miscommunication is an early and causal trigger of hepatic insulin resistance and steatosis","volume":"77","author":"Beaulant","year":"2022","journal-title":"J Hepatol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjw004","article-title":"Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver","volume":"8","author":"Theurey","year":"2016","journal-title":"J Mol Cell Biol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"165525","DOI":"10.1016\/j.bbadis.2019.08.001","article-title":"Structure-toxicity relationships of saturated and unsaturated free fatty acids for elucidating the lipotoxic effects in human EndoC-\u03b2H1 beta-cells","volume":"1865","author":"Pl\u00f6tz","year":"2019","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01554","article-title":"The distinct effects of palmitic and oleic acid on pancreatic beta cell function: The elucidation of associated mechanisms and effector molecules","volume":"9","author":"Nemecz","year":"2018","journal-title":"Front Pharmacol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200604016","article-title":"Structural and functional features and significance of the physical linkage between ER and mitochondria","volume":"174","author":"Csordas","year":"2006","journal-title":"J Cell Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-025-01668-z","article-title":"Endoplasmic reticulum-mitochondria contacts are prime hotspots of phospholipid peroxidation driving ferroptosis","volume":"27","author":"Sassano","year":"2025","journal-title":"Nat Cell Biol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201541504","article-title":"Fate1 antagonizes calcium- and drug-induced apoptosis by uncoupling ER and mitochondria","volume":"17","author":"Doghman-Bouguerra","year":"2016","journal-title":"EMBO Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-017-0033-z","article-title":"Splics: A split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition","volume":"25","author":"Cieri","year":"2018","journal-title":"Cell Death Differ"},{"key":"B50","doi-asserted-by":"publisher","first-page":"6069","DOI":"10.1038\/s41467-020-19892-6","article-title":"An expanded palette of improved Splics reporters detects multiple organelle contacts in vitro and in vivo","volume":"11","author":"Vallese","year":"2020","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1629568","article-title":"The role of mitochondria-associated er membranes in disease pathology: Protein complex and therapeutic targets","volume":"13","author":"Zhang","year":"2025","journal-title":"Front Cell Dev Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182027","article-title":"Reduction of endoplasmic reticulum- mitochondria interactions in beta cells from patients with type 2 diabetes","volume":"12","author":"Thivolet","year":"2017","journal-title":"PLoS One"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3829-8","article-title":"Disruption of calcium transfer from er to mitochondria links alterations of mitochondria-associated er membrane integrity to hepatic insulin resistance","volume":"59","author":"Rieusset","year":"2016","journal-title":"Diabetologia"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.11.009","article-title":"Palmitic and oleic acid: The yin and yang of fatty acids in type 2 diabetes mellitus","volume":"29","author":"Palomer","year":"2018","journal-title":"Trends Endocrinol Metab"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-019-01867-3","article-title":"Oleic acid protects insulin-secreting ins-1e cells against palmitic acid-induced lipotoxicity along with an amelioration of er stress","volume":"64","author":"Liu","year":"2019","journal-title":"Endocrine"},{"key":"B56","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/s41467-023-36298-2","article-title":"The p97-ubxd8 complex regulates er-mitochondria contact sites by altering membrane lipid saturation and composition","volume":"14","author":"Ganji","year":"2023","journal-title":"Nat Commun"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1042\/BST0360343","article-title":"Oxidative stress: The vulnerable beta-cell","volume":"36","author":"Lenzen","year":"2008","journal-title":"Biochem Soc Trans"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.568329","article-title":"Peroxiredoxin 4 improves insulin biosynthesis and glucose-induced insulin secretion in insulin-secreting ins-1e cells","volume":"289","author":"Mehmeti","year":"2014","journal-title":"J Biol Chem"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1530\/JME-15-0232","article-title":"Oxidative and endoplasmic reticulum stress in beta-cell dysfunction in diabetes","volume":"56","author":"Hasnain","year":"2016","journal-title":"J Mol Endocrinol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1186\/s12864-020-07003-0","article-title":"Combined transcriptome and proteome profiling of the pancreatic beta-cell response to palmitate unveils key pathways of beta-cell lipotoxicity","volume":"21","author":"Lytrivi","year":"2020","journal-title":"BMC Genomics"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.01.017","article-title":"Regulation of calcium homeostasis by er redox: A close-up of the er\/mitochondria connection","volume":"429","author":"Chernorudskiy","year":"2017","journal-title":"J Mol Biol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4004","article-title":"Ero1alpha regulates ca(2+) fluxes at the endoplasmic reticulum-mitochondria interface (mam)","volume":"16","author":"Anelli","year":"2012","journal-title":"Antioxid Redox Signal"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1709284","article-title":"Endoplasmic reticulum oxidoreductin 1alpha as a potential therapeutic target in diseases: From oxidative protein folding to pathophysiological mechanisms","volume":"16","author":"He","year":"2025","journal-title":"Front Pharmacol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.040","article-title":"Redox nanodomains are induced by and control calcium signaling at the er-mitochondrial interface","volume":"63","author":"Booth","year":"2016","journal-title":"Mol Cell"},{"key":"B65","doi-asserted-by":"publisher","first-page":"11010","DOI":"10.1038\/s41467-025-66115-x","article-title":"Glp-1r associates with vapb and sphkap at ermcss to regulate beta-cell mitochondrial remodelling and function","volume":"16","author":"Austin","year":"2025","journal-title":"Nat Commun"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1852671\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:41:20Z","timestamp":1784785280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1852671\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":65,"alternative-id":["10.3389\/fendo.2026.1852671"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1852671","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"article-number":"1852671"}}