{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T14:12:03Z","timestamp":1770991923950,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC306"],"award-info":[{"award-number":["EXC306"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC1182"],"award-info":[{"award-number":["CRC1182"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRU303"],"award-info":[{"award-number":["CRU303"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["0315892B"],"award-info":[{"award-number":["0315892B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G &gt; T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system.<\/jats:p>","DOI":"10.3390\/ijms22031006","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T12:16:18Z","timestamp":1611144978000},"page":"1006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-656X","authenticated-orcid":false,"given":"Paul","family":"Schilf","sequence":"first","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0692-2105","authenticated-orcid":false,"given":"Axel","family":"K\u00fcnstner","sequence":"additional","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Institute of Cardiogenetics, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Olbrich","sequence":"additional","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6290-3593","authenticated-orcid":false,"given":"Silvio","family":"Waschina","sequence":"additional","affiliation":[{"name":"Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, 24098 Kiel, 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Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malte","family":"Seutter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3855-6683","authenticated-orcid":false,"given":"Katja","family":"Bieber","sequence":"additional","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Hellberg","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Sina","sequence":"additional","affiliation":[{"name":"Institute of Nutritional Medicine, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tam\u00e1s","family":"Laskay","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Rupp","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Microbiology, University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf J.","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Center for Research on Inflammation of the Skin (CRIS), University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Detlef","family":"Zillikens","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Center for Research on Inflammation of the Skin (CRIS), University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-4521","authenticated-orcid":false,"given":"Hauke","family":"Busch","sequence":"additional","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Institute of Cardiogenetics, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Center for Research on Inflammation of the Skin (CRIS), University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6701-048X","authenticated-orcid":false,"given":"Christian D.","family":"Sadik","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Center for Research on Inflammation of the Skin (CRIS), University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misa","family":"Hirose","sequence":"additional","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Center for Research on Inflammation of the Skin (CRIS), University of Luebeck, 23562 Luebeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saleh M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Luebeck Institute of Experimental Dermatology, University of Luebeck, 23562 Luebeck, Germany"},{"name":"Center for Research on Inflammation of the Skin (CRIS), University of Luebeck, 23562 Luebeck, Germany"},{"name":"College of Medicine and Sharjah Institute for Medical Research, University of Sharjah, 27272 Sharjah, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/0092-8674(88)90218-8","article-title":"Familial Mitochondrial Encephalomyopathy (MERRF): Genetic, Pathophysiological, and Biochemical Characterization of a Mitochondrial DNA Disease","volume":"55","author":"Wallace","year":"1988","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev.genet.39.110304.095751","article-title":"A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine","volume":"39","author":"Wallace","year":"2005","journal-title":"Annu. 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