{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:07:05Z","timestamp":1779444425323,"version":"3.53.1"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Hashimoto\u2019s thyroiditis (HT) is a common autoimmune disorder characterized by chronic inflammation and metabolic alterations. Mitochondria-derived peptides (MDPs), particularly mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c), have emerged as key regulators of cellular metabolism, insulin sensitivity, oxidative stress, and inflammatory responses. This study aimed to investigate the association between circulating MOTS-c levels and HT and to explore its potential role in thyroid autoimmunity and metabolic regulation. Methods: In this cross-sectional study, patients diagnosed with HT (n: 90) were compared with age- and sex-matched healthy controls (n: 90). Results: A total of 180 participants were included, comprising 90 patients with HT and 90 age- and sex-matched healthy controls. Circulating MOTS-c levels were significantly lower in patients with HT compared to controls (p &lt; 0.001). MOTS-c levels demonstrated significant inverse correlations with body mass index, fasting glucose, HbA1c, HOMA-IR, thyroid-stimulating hormone, C-reactive protein, and thyroid autoantibody levels (all p &lt; 0.05). In subgroup analyses, these associations remained significant within the HT cohort, particularly for HOMA-IR and thyroid autoantibodies. Multivariable regression analysis identified HT (\u03b2 = \u221230.04, p &lt; 0.001) and HOMA-IR (\u03b2 = \u22120.85, p &lt; 0.001) as independent determinants of reduced circulating MOTS-c levels. Levothyroxine (LT4) use was not associated with significant differences in MOTS-c concentrations. Conclusions: Circulating MOTS-c levels are markedly reduced in patients with HT and are independently associated with insulin resistance and autoimmune burden. These findings suggest that impaired mitochondrial signaling may play a role in the pathophysiology of thyroid autoimmunity and highlight MOTS-c as a promising biomarker linking metabolic dysfunction and immune dysregulation.<\/jats:p>","DOI":"10.3390\/jcm15114002","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T09:17:09Z","timestamp":1779441429000},"page":"4002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced Circulating MOTS-c Levels in Hashimoto\u2019s Thyroiditis Reflect Integrated Autoimmune and Metabolic Dysregulation: A Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Hani\u015fe Ozkan","family":"Sonay","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, Health Sciences University, 34303 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9126-0363","authenticated-orcid":false,"given":"Eda Nur","family":"Duran","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Pervari State Hospital, 56700 Siirt, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5117-528X","authenticated-orcid":false,"given":"Murvet","family":"Algemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Kanuni Sultan Suleyman Training and Research Hospital, Health Sciences University, 34303 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berrak","family":"Sahtiyanci","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Istanbul Physical Therapy and Rehabilitation Training and Research Hospital, Health Sciences University, 34303 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irem Kirac","family":"Utku","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Geriatrics, Tekirda\u011f Dr. \u0130smail Fehmi Cumal\u0131o\u011flu City Hospital, 59030 Tekirda\u011f, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"\u00c7oki\u00e7li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Istanbul Medipol University, 34810 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4735-4091","authenticated-orcid":false,"given":"Naile Fevziye","family":"Misirlioglu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34403 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gonul","family":"Simsek","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Istanbul Atlas University, 34403 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-8498","authenticated-orcid":false,"given":"Hafize","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34403 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omur","family":"Tabak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanuni Sultan Suleyman Training and Research Hospital, Health Sciences University, 34303 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101367","DOI":"10.1016\/j.beem.2019.101367","article-title":"Hashimotos\u2019 Thyroiditis: Epidemiology, Pathogenesis, Clinic and Therapy","volume":"33","author":"Ragusa","year":"2019","journal-title":"Best Pract. 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