{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:53:07Z","timestamp":1792443187709,"version":"4.5.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"16","license":[{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      The outer mitochondrial membrane protein Miro1 is a crucial player in mitochondrial dynamics and calcium homeostasis. Recent evidence indicated that Miro1 mediates calcium-induced mitochondrial shape transition, which is a prerequisite for the initiation of mitophagy. Moreover, altered Miro1 protein levels have emerged as a shared feature of monogenic and sporadic Parkinson's disease (PD), but, so far, no disease-associated variants in\n                      <jats:italic toggle=\"yes\">RHOT1<\/jats:italic>\n                      have been identified. Here, we aim to explore the genetic and functional contribution of\n                      <jats:italic toggle=\"yes\">RHOT1<\/jats:italic>\n                      mutations to PD in patient-derived cellular models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      For the first time, we describe heterozygous\n                      <jats:italic toggle=\"yes\">RHOT1<\/jats:italic>\n                      mutations in two PD patients (het c.815G&gt;A; het c.1348C&gt;T) and identified mitochondrial phenotypes with reduced mitochondrial mass in patient fibroblasts. Both mutations led to decreased endoplasmic reticulum-mitochondrial contact sites and calcium dyshomeostasis. As a consequence, energy metabolism was impaired, which in turn caused increased mitophagy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>\n                      Our study provides functional evidence that\n                      <jats:italic toggle=\"yes\">ROTH1<\/jats:italic>\n                      is a genetic risk factor for PD, further implicating Miro1 in calcium homeostasis and mitochondrial quality control.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2018.7718","type":"journal-article","created":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T03:19:00Z","timestamp":1563160740000},"page":"1213-1234","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":88,"title":["Mutations in\n                    <i>RHOT1<\/i>\n                    Disrupt Endoplasmic Reticulum\u2013Mitochondria Contact Sites Interfering with Calcium Homeostasis and Mitochondrial Dynamics in Parkinson's Disease"],"prefix":"10.1177","volume":"31","author":[{"given":"Dajana","family":"Grossmann","sequence":"first","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Berenguer-Escuder","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Estelle","family":"Bellet","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Scheibner","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, Center of Neurology and Hertie-Institute for Clinical Brain Research, University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Bohler","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Massart","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Rapaport","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Biochemistry (IFIB), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Skupin","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."},{"name":"National Biomedical Computation Resource, University of California San Diego, La Jolla, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aymeric","family":"Fouquier d'H\u00e9rou\u00ebl","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu","family":"Sharma","sequence":"additional","affiliation":[{"name":"Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Ghelfi","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Rakovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics, University of L\u00fcbeck, L\u00fcbeck, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lichtner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Helmholtz Zentrum M\u00fcnchen GmbH, Neuherberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Antony","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Glaab","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"May","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Stefan","family":"Dimmer","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Biochemistry (IFIB), University of T\u00fcbingen, T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Catherine","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Diseases, Center of Neurology and Hertie-Institute for Clinical Brain 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