MOTS-c Source

Readout · 07

MOTS-c peptide references and sources

Every quantitative claim in this digest maps to a numbered entry below. Peer-reviewed studies and FDA regulatory sources.

How to read this list

Entries 1–15 are the peer-reviewed studies — predominantly animal and cell research, with the human data limited to observational biomarker associations. Entries 16–18 are the FDA sources behind the regulatory and 503A statements on the MOTS-c legal status and 503A access page. Each entry carries a DOI or PMID and a direct link. Inline markers such as [1] throughout the site point to the matching entry here.

  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. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose. Physiol Rep. 2022;10(13):e15377. ↗
  6. Kumagai H, Coelho AR, Wan J, Mehta HH, Yen K, Huang A, Zempo H, Fuku N, Maeda S, Oliveira PJ, Cohen P, Kim SJ. MOTS-c reduces myostatin and muscle atrophy signaling. Am J Physiol Endocrinol Metab. 2021;320(4):E680-E690. ↗
  7. Kim SJ, Miller B, Kumagai H, Silverstein AR, Flores M, Yen K. Mitochondrial-derived peptides in aging and age-related diseases. GeroScience. 2020;43(3):1113-1121. ↗
  8. Kim SJ, Xiao J, Wan J, Cohen P, Yen K. Mitochondrially derived peptides as novel regulators of metabolism. J Physiol. 2017;595(21):6613-6621. ↗
  9. 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. ↗
  10. 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(11-12):925-934. ↗
  11. Elhusseiny R, Ihsan M, Bellefroid T, Farooq A, Racinais S, Deldicque L. Mitochondrial-derived peptides MOTS-c and humanin attenuate dexamethasone-induced atrophy in human skeletal muscle cells. Physiol Rep. 2026;14(1):e70791. ↗
  12. Jia H, Zhou LC, Chen YF, Zhang W, Qi W, Wang P, Huang X, Guo JW, Hou WF, Zhang RR, Zhou JJ, Zhang DW. Mitochondria-encoded peptide MOTS-c participates in plasma membrane repair by facilitating the translocation of TRIM72 to membrane. Theranostics. 2024;14(14):5645-5662. ↗
  13. Kumagai H, Kim SJ, Miller B, Natsume T, Wan J, et al. Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration. Am J Physiol Endocrinol Metab. 2024;326(2):E207-E218. ↗
  14. Shen Z, Lu P, Jin W, et al. MOTS-c Promotes Glycolysis via AMPK-HIF-1alpha-PFKFB3 Pathway to Ameliorate Cardiopulmonary Bypass-induced Lung Injury. Am J Respir Cell Mol Biol. 2025;72(5):512-525. ↗
  15. Li K, Yang T, Chen F, et al. MOTS-c attenuates mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via an Nrf2-Dependent Mechanism. Free Radic Biol Med. 2025;237:1-13. ↗
  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. ↗
  17. U.S. Food and Drug Administration. Human Drug Compounding: Section 503A traditional compounding pharmacies and Section 503B outsourcing facilities (program overview). ↗
  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). ↗