# MOTS-c peptide References: Cited Studies and Sources

> MOTS-c peptide references: the full citation list behind this digest — PubMed-indexed studies on mechanism, exercise, and muscle preservation, plus the FDA sources for the regulatory and 503A status.

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](/legal-status) 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.

## 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] 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. https://pubmed.ncbi.nlm.nih.gov/35808870/
[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. https://pubmed.ncbi.nlm.nih.gov/33554779/
[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. https://pubmed.ncbi.nlm.nih.gov/32910336/
[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. https://pubmed.ncbi.nlm.nih.gov/28574175/
[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. https://pubmed.ncbi.nlm.nih.gov/39559755/
[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. https://pubmed.ncbi.nlm.nih.gov/39111290/
[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. https://pubmed.ncbi.nlm.nih.gov/41732124/
[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. https://pubmed.ncbi.nlm.nih.gov/39267782/
[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. https://pubmed.ncbi.nlm.nih.gov/38170165/
[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. https://pubmed.ncbi.nlm.nih.gov/40035775/
[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. https://pubmed.ncbi.nlm.nih.gov/41043625/
[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. 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. Human Drug Compounding: Section 503A traditional compounding pharmacies and Section 503B outsourcing facilities (program overview). https://www.fda.gov/drugs/guidance-compliance-regulatory-information/human-drug-compounding
[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). https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026

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A thermographic read of the MOTS-c record — each finding logged at the temperature its data actually run and the research-use and FDA standing read before anything else; no clinic behind the instrument and nothing here dispensed or sold.