{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:17:54Z","timestamp":1776482274472,"version":"3.51.2"},"reference-count":17,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Scholarship Council (CSC) Grant","award":["310030_185219"],"award-info":[{"award-number":["310030_185219"]}]},{"name":"China Scholarship Council (CSC) Grant","award":["320030_189252"],"award-info":[{"award-number":["320030_189252"]}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Foundation","doi-asserted-by":"publisher","award":["310030_185219"],"award-info":[{"award-number":["310030_185219"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Foundation","doi-asserted-by":"publisher","award":["320030_189252"],"award-info":[{"award-number":["320030_189252"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"die Stiftung f\u00fcr Leberkrankheiten","award":["310030_185219"],"award-info":[{"award-number":["310030_185219"]}]},{"name":"die Stiftung f\u00fcr Leberkrankheiten","award":["320030_189252"],"award-info":[{"award-number":["320030_189252"]}]},{"name":"Stiftung f\u00fcr Leberkrankheiten (Swiss Liver Foundation)","award":["310030_185219"],"award-info":[{"award-number":["310030_185219"]}]},{"name":"Stiftung f\u00fcr Leberkrankheiten (Swiss Liver Foundation)","award":["320030_189252"],"award-info":[{"award-number":["320030_189252"]}]},{"name":"Gottfried","award":["310030_185219"],"award-info":[{"award-number":["310030_185219"]}]},{"name":"Gottfried","award":["320030_189252"],"award-info":[{"award-number":["320030_189252"]}]},{"name":"Julia Bangerter-Rhyner Foundation","award":["310030_185219"],"award-info":[{"award-number":["310030_185219"]}]},{"name":"Julia Bangerter-Rhyner Foundation","award":["320030_189252"],"award-info":[{"award-number":["320030_189252"]}]},{"name":"Swiss Academy of Medical Sciences (SAMS)","award":["310030_185219"],"award-info":[{"award-number":["310030_185219"]}]},{"name":"Swiss Academy of Medical Sciences (SAMS)","award":["320030_189252"],"award-info":[{"award-number":["320030_189252"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The interaction between the mitochondria and the endoplasmic reticulum (ER) is essential for hepatocyte function. An increase in ER\u2013mitochondria contacts (ERMCs) is associated with various metabolic diseases. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes, and its progressive form non-alcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma. However, the role of ERMCs in the progression of NAFL to NASH is still unclear. We assessed whether ERMCs could correlate with NAFLD severity. We used a proximity ligation assay to measure the abundance of ERMCs in liver biopsies from patients with biopsy-proven NAFLD (n = 48) and correlated the results with histological and metabolic syndrome (MetS) features. NAFLD patients were included according to inclusion and exclusion criteria, and then assigned to NAFL (n = 9) and NASH (n = 39) groups. ERMCs density could discriminate NASH from NAFL (sensitivity 61.5%, specificity 100%). ERMCs abundance correlated with hepatocellular ballooning. Moreover, the density of ERMCs increased with an increase in the number of MetS features. In conclusion, ERMCs increased from NAFL to NASH, in parallel with the number of MetS features, supporting a role for this interaction in the pathophysiology of NASH.<\/jats:p>","DOI":"10.3390\/ijms23158348","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T20:49:28Z","timestamp":1659041368000},"page":"8348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Endoplasmic Reticulum and Mitochondria Contacts Correlate with the Presence and Severity of NASH in Humans"],"prefix":"10.3390","volume":"23","author":[{"given":"Chaonan","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Department for BioMedical Research, Hepatology, University of Bern, 3012 Bern, Switzerland"},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-6746","authenticated-orcid":false,"given":"Eric","family":"Felli","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Department for BioMedical Research, Hepatology, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-4949","authenticated-orcid":false,"given":"Naomi Franziska","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Graduate School for Health Sciences, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Berzigotti","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Department for BioMedical Research, Hepatology, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-4089","authenticated-orcid":false,"given":"Jordi","family":"Gracia-Sancho","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland"},{"name":"Department for BioMedical Research, Hepatology, University of Bern, 3012 Bern, Switzerland"},{"name":"Liver Vascular Biology Research Group, CIBEREHD, IDIBAPS Research Institute, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-1346","authenticated-orcid":false,"given":"Jean-Fran\u00e7ois","family":"Dufour","sequence":"additional","affiliation":[{"name":"Department for BioMedical Research, Hepatology, University of Bern, 3012 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1427","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":"ref_2","doi-asserted-by":"crossref","first-page":"3279","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":"ref_3","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nature10988","article-title":"Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes","volume":"485","author":"Wang","year":"2012","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cld.2017.08.003","article-title":"The Natural History of Nonalcoholic Fatty Liver Disease-An Evolving View","volume":"22","author":"Lindenmeyer","year":"2018","journal-title":"Clin Liver Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"614","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":"ref_7","first-page":"205","article-title":"Sulforaphane improves disrupted ER-mitochondria interactions and suppresses exaggerated hepatic glucose production","volume":"461","author":"Tubbs","year":"2018","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"129","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":"ref_9","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Stacchiotti, A., Favero, G., Lavazza, A., Garcia-Gomez, R., Monsalve, M., and Rezzani, R. (2018). Perspective: Mitochondria-ER Contacts in Metabolic Cellular Stress Assessed by Microscopy. Cells, 8.","DOI":"10.3390\/cells8010005"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E1053","DOI":"10.1152\/ajpendo.00271.2020","article-title":"Mitochondria-associated ER membranes in glucose homeostasis and insulin resistance","volume":"319","author":"Townsend","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/hep4.1012","article-title":"Hepatic Inositol 1,4,5 Trisphosphate Receptor Type 1 Mediates Fatty Liver","volume":"1","author":"Feriod","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and disease consequences of nonalcoholic fatty liver disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"(2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol., 64, 1388\u20131402.","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1002\/hep.25889","article-title":"Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients","volume":"56","author":"Bedossa","year":"2012","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.jhep.2019.12.008","article-title":"Clinical validation of the FLIP algorithm and the SAF score in patients with non-alcoholic fatty liver disease","volume":"72","author":"Nascimbeni","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Unal, I. (2017). Defining an Optimal Cut-Point Value in ROC Analysis: An Alternative Approach. Comput. Math. Methods Med., 2017.","DOI":"10.1155\/2017\/3762651"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8348\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:58:17Z","timestamp":1760140697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,28]]},"references-count":17,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158348"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158348","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,28]]}}}