{"schemaVersion":"wpf-profile-export-v1","exportedAt":"2026-09-18T15:17:31.044Z","profile":{"slug":"mots-c","name":"MOTS-c","aliases":["Mitochondrial ORF of the 12S rRNA-c","MOTS-c peptide"],"category":"Mitochondrial-derived peptide"},"synthesis":{"mechanism":"MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA region. Experimental work links it to cellular stress responses, AMPK-related metabolism, nuclear signaling, exercise adaptation, and age-associated physiology.","evidence":"The field includes extensive cell and animal research plus human observational studies of endogenous MOTS-c levels and genetic variants. Evidence that administered synthetic MOTS-c safely improves clinical outcomes in humans remains insufficient.","safety":"Endogenous association studies do not establish the safety of exogenous administration. 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Relationship to named compound is explicitly classified.","sourceType":"peer_reviewed_research","claimSupported":"This source contributes human_interventional evidence concerning Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.","supportNature":"contextualizes","qualification":"Context source concerns a parent peptide, related analog, pathway, detection method, or broader class and must not be treated as direct evidence for the named compound.","verificationStatus":"verified","publicationStatus":"published","addedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","machineActor":"wpf-eight-corpus-expansion-2026-09-08","reviewedById":"0bf5b853-ea8b-4aa3-bffe-2af0fdd75150","canonicalSourceIdentity":"doi:10.1007/s40279-026-02437-0","sourceIdentityId":null,"sourceStatus":"active","sourceContentHash":null,"sourceVersion":1,"retrievedAt":"2026-09-08T19:33:45.384Z","retrievalProvider":"NCBI PubMed","retrievalPayloadRef":"wpf:mots-c:wave2:2026-09-08","evidenceLane":"human_interventional","extractionPayload":{"limitations":["Context source concerns a parent peptide, related analog, pathway, detection method, or broader class and must not be treated as direct evidence for the named compound."],"studyDesign":"Human interventional or clinical study","sourceStrength":{"note":"Automated structured-metadata baseline; full-text risk-of-bias review may revise this rating.","grade":"C","score":63,"version":"WPF-ESR-1.0","dimensions":{"authority":78,"reporting":68,"directness":45,"replication":45,"designAndBias":68,"populationRelevance":78},"provisional":true},"directCompoundEvidence":false,"relationshipToNamedCompound":"parent_analog_pathway_or_regulatory_context"},"provenancePayload":{"doi":"10.1007/s40279-026-02437-0","pmid":"41966639","retrievedFrom":"NCBI PubMed"},"validationGates":{"sourceVerified":true,"ownerAuthorized":true,"identityResolved":true,"relationshipClassified":true,"neutralLanguageVerified":true},"engineState":"promoted_internal","engineRunId":null,"createdAt":"2026-09-08T19:33:45.384Z","updatedAt":"2026-09-08T19:33:45.384Z"},{"id":"1bb72cf3f9d3557d5b2ffcce04f4d166","peptideId":"85239683-58ff-4847-8d53-ce1e5c71679b","title":"Circulating Mitochondrial Open Reading Frame of the 12S Ribosomal RNA Type-c Is Higher in Acute Coronary Syndrome and Is a Prognostic Biomarker for Major Cardiac Events in Patients With Acute Myocardial Infarction: A Case-Control Study.","sourceUrl":"https://pubmed.ncbi.nlm.nih.gov/41368821/","evidenceTier":"phase_1_2","summary":"In vitro studies demonstrated that oxidative stress induces MOTS-c levels and MOTS-c treatment reduces hypoxia-induced oxidative stress through activating antioxidants. CONCLUSIONS: The circulating MOTS-c is associated with an increased r …","authors":"Cao P, Wang B, Zhang N, Yang J, Tong Q, Gong Z.","publishingOrg":null,"publicationYear":2025,"doi":"10.1161/JAHA.125.041905","pubmedId":"41368821","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Here, we demonstrate CK2 is a direct and functional target of MOTS-c. ...Notably, a naturally occurring MOTS-c variant, K14Q MOTS-c, has reduced binding to CK2 …","authors":"Kumagai H, Kim SJ, Miller B, Zempo H, Tanisawa K, Natsume T, Lee SH, Wan J, Leelaprachakul N, Kumagai ME, Ramirez R 2nd, Mehta HH, Cao K, Oh TJ, Wohlschlegel JA, Sha J, Nishida Y, Fuku N, Dobashi S, Miyamoto-Mikami E, Takaragawa M, Fuku M, Yoshihara T, Naito H, Kawakami R, Torii S, Midorikawa T, Oka K, Hara M, Iwasaka C, Yamada Y, Higaki Y, Tanaka K, Yen K, Cohen P.","publishingOrg":null,"publicationYear":2024,"doi":"10.1016/j.isci.2024.111212","pubmedId":"39559755","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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Here, we show that MOTS-c, a peptide encoded in the mitochondrial genome …","authors":"Kim KH, Son JM, Benayoun BA, Lee C.","publishingOrg":null,"publicationYear":2018,"doi":"10.1016/j.cmet.2018.06.008","pubmedId":"29983246","jurisdiction":null,"dateAccessed":"2026-09-08T19:33:45.384Z","editorialNotes":"AI-assisted corpus expansion authorized by owner on 2026-09-08. 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