MOTS-c Compound

Research digest · Sources

MOTS-c peptide references: every source behind this digest.

The peer-reviewed studies, reviews, and FDA regulatory pages cited across this site, with DOIs, PMIDs, and links to the originals.

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Every quantitative claim on this site maps to a numbered citation below. References 1–15 are the peer-reviewed MOTS-c literature — founding studies, mechanism papers, biomarker observations, and reviews. References 16–18 are the FDA regulatory sources behind the MOTS-c legal status and 503A category page. Where a study reported a species, dose, or statistic, that detail is traceable here to its source. Links resolve to PubMed or the publisher; FDA references link to the relevant FDA.gov pages.

  1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. ↗
  2. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. ↗
  3. Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018;28(3):516-524.e7. ↗
  4. Wan W, Zhang L, Lin Y, Rao X, Wang X, Hua F, Ying J. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. J Transl Med. 2023;21(1):36. ↗
  5. Kim SJ, Miller B, Mehta HH, Xiao J, Wan J, Arpawong TE, Yen K, Cohen P. The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity. Physiol Rep. 2019;7(13):e14171. ↗
  6. Du C, Zhang C, Wu W, Liang Y, Wang A, Wu S, Zhao Y, Hou L, Ning Q, Luo X. Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes. 2018;19(5):1058-1064. ↗
  7. Zempo H, Kim SJ, Fuku N, et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY). 2021;13(2):1801-1817. ↗
  8. Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023;13(1):125. ↗
  9. Yi X, Hu G, Yang Y, Li J, Jin J, Chang B. Role of MOTS-c in the regulation of bone metabolism. Front Physiol. 2023;14:1149120. ↗
  10. Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023;14:1120533. ↗
  11. Tekin S, Bir LS, Avci E, et al. Comparison of Serum Mitochondrial Open Reading Frame of the 12S rRNA-c (MOTS-c) Levels in Patients With Multiple Sclerosis and Healthy Controls. Cureus. 2022;14(7):e26981. ↗
  12. Fuku N, Pareja-Galeano H, Zempo H, et al. The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity? Aging Cell. 2015;14(6):921-923. ↗
  13. Kumagai H, Kim SJ, Miller B, et al. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. iScience. 2024;27(11):111212. ↗
  14. Bolignano D, Greco M, Presta P, Duni A, et al. The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study. Blood Purif. 2024;53(9-10):1-12. ↗
  15. Pham T, Taberner A, Hickey A, Han JC. Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart. Front Physiol. 2025;16:1602271. ↗
  16. U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. FDA, Human Drug Compounding (verified 2026-05-29). ↗
  17. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks. FDA, Human Drug Compounding (list entries effective 2023-09-29; verified 2026-05-29). ↗
  18. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee (agenda lists BPC-157, KPV, TB-500, and MOTS-c as bulk drug substances being considered for inclusion on the 503A Bulks List). FDA Advisory Committee Calendar (verified 2026-05-29). ↗