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MOTS-c peptide reading list

The original experiments, the broader reviews, and the dated regulatory documents collected in one place.

Return to the discovery inventoryCompare the blood studies

Discovery and mechanism

The discovery shelf begins with Lee and colleagues’ 2015 metabolic experiments, followed by the 2018 nuclear stress-response study and the 2024 direct-binding work on CK2. Together they show how the MOTS-c peptide’s proposed mechanism became more specific.

The 2021 exercise paper supplies the physical-capacity experiments. The 2023 stress, metabolism and aging review is the broadest overview in this list.

Human blood observations

Read the pediatric insulin-resistance report beside the childhood vascular-function study. Then try the chronic hemodialysis cohort. I favour that sequence because the dialysis result complicates a simple interpretation of low and high blood concentrations.

The comparison of the human studies preserves their different populations. All measured endogenous MOTS-c rather than treating people with it.

FDA documents

The 503A bulk-substance framework, safety-risk page and July 23-24, 2026 advisory meeting notice belong in a separate regulatory file. The citations below record their verification date. The legal-status page explains the limits of that pre-meeting record.

  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. 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. ↗
  6. Luo YH, Xie L, Li JY, Xie Y, Li MQ, Zhou L. Serum MOTS-C Levels are Decreased in Obese Children and Associated with Vascular Endothelial Function. Diabetes Metab Syndr Obes. 2023;16:1125-1133. ↗
  7. Lu H, Wei M, Zhai Y, Li Q, Ye Z, Wang L, Luo W, Chen J, Lu Z. MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med (Berl). 2019;97(4):473-485. ↗
  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. 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. ↗
  10. 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. ↗
  11. 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):779-789. ↗
  12. 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. ↗
  13. Parseh S, Shakerian S, Tabandeh MR, Habibi A. An 8-week study on the effects of high and moderate-intensity interval exercises on mitochondrial MOTS-C changes and their relation to metabolic markers in male diabetic sand rats. Diabetes Res Clin Pract. 2024;211:111656. ↗
  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(6):615-628. ↗
  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;238:1-14. ↗
  16. U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. FDA.gov (verified 2026-05-29). Establishes the 503A/503B compounding framework, the bulk-substance eligibility rules, the public nomination process, and the role of the Pharmacy Compounding Advisory Committee (PCAC). ↗
  17. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks. FDA.gov (verified 2026-05-29). The published list of nominated bulk drug substances FDA identified as raising significant safety risks for 503A compounding. ↗
  18. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee. FDA Advisory Committee Calendar (verified 2026-05-29). Lists BPC-157, KPV, TB-500, and MOTS-c as bulk drug substances being considered for inclusion on the 503A Bulks List; a scheduled discussion, not a decision. ↗