# MOTS-c peptide References: The Cited Literature and Regulatory Sources

> MOTS-c peptide references: the full citation list behind this digest — PubMed-indexed studies, reviews, and FDA regulatory sources, with DOIs and links.

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

## How to Read This List

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](/legal-status) 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.

## References

[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. https://pubmed.ncbi.nlm.nih.gov/25738459/
[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. https://pubmed.ncbi.nlm.nih.gov/33473109/
[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. https://pubmed.ncbi.nlm.nih.gov/29983246/
[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. https://pubmed.ncbi.nlm.nih.gov/36670507/
[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. https://pubmed.ncbi.nlm.nih.gov/31293078/
[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. https://pubmed.ncbi.nlm.nih.gov/29691953/
[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. https://pubmed.ncbi.nlm.nih.gov/33468709/
[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. https://pubmed.ncbi.nlm.nih.gov/36677050/
[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. https://pubmed.ncbi.nlm.nih.gov/37200834/
[10] Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023;14:1120533. https://pubmed.ncbi.nlm.nih.gov/36936170/
[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. https://pubmed.ncbi.nlm.nih.gov/35989823/
[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. https://pubmed.ncbi.nlm.nih.gov/26289118/
[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. https://pubmed.ncbi.nlm.nih.gov/39559755/
[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. https://pubmed.ncbi.nlm.nih.gov/39111290/
[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. https://pubmed.ncbi.nlm.nih.gov/40661667/
[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). https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act
[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). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
[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). https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026

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An exhibition-wall reading of the mitochondrial-derived MOTS-c peptide literature — each study hung as its own plate and cited, the large search demand held apart from the empty human-trial wall, and the FDA research-only standing and July-2026 PCAC agenda noted before anything else; no clinic curates this room and nothing here is dispensed or sold.