MOTS-c peptide references and citations

Peer-Reviewed Studies

The studies below are the primary literature behind the mechanism, metabolic, exercise, bone, oncology, and membrane-repair claims summarized across this site. Each is identified by author, journal, year, DOI, and PubMed ID.

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 Metabolism. 2015;21(3):443-454. DOI: 10.1016/j.cmet.2015.02.009. PMID: 25738459. https://pubmed.ncbi.nlm.nih.gov/25738459/

1. 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. Nature Communications. 2021;12(1):470. DOI: 10.1038/s41467-020-20790-0. PMID: 33473109. https://pubmed.ncbi.nlm.nih.gov/33473109/

1. 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 Metabolism. 2018;28(3):516-524.e7. DOI: 10.1016/j.cmet.2018.06.008. PMID: 29983246. https://pubmed.ncbi.nlm.nih.gov/29983246/

1. 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. Journal of Translational Medicine. 2023;21(1):36. DOI: 10.1186/s12967-023-03885-2. PMID: 36670507. https://pubmed.ncbi.nlm.nih.gov/36670507/

1. Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. International Journal of Molecular Sciences. 2022;23(19):11991. DOI: 10.3390/ijms231911991. PMID: 36233287. https://pubmed.ncbi.nlm.nih.gov/36233287/

1. Lee C. Nuclear transcriptional regulation by mitochondrial-encoded MOTS-c. Molecular and Cellular Oncology. 2019;6(2):e1549464. DOI: 10.1080/23723556.2018.1549464. PMID: 31131297. https://pubmed.ncbi.nlm.nih.gov/31131297/

1. Ming W, Lu G, Sha X, et al. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochemical and Biophysical Research Communications. 2016;476(4):412-419. DOI: 10.1016/j.bbrc.2016.05.135. PMID: 27237975. https://pubmed.ncbi.nlm.nih.gov/27237975/

1. Kim SJ, Xiao J, Wan J, Cohen P, Yen K. Mitochondrially derived peptides as novel regulators of metabolism. The Journal of Physiology. 2017;595(21):6613-6621. DOI: 10.1113/jp274472. PMID: 28574175. https://pubmed.ncbi.nlm.nih.gov/28574175/

1. Kumagai H, Kim SJ, Miller B, et al. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. iScience. 2024;27(12):111212. DOI: 10.1016/j.isci.2024.111212. PMID: 39559755. https://pubmed.ncbi.nlm.nih.gov/39559755/

1. 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 Purification. 2024;53(11-12):874-884. DOI: 10.1159/000540303. PMID: 39111290. https://pubmed.ncbi.nlm.nih.gov/39111290/

1. Kong BS, Lee C, Cho YM. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. Diabetes and Metabolism Journal. 2023;47(3):315-324. DOI: 10.4093/dmj.2022.0333. PMID: 36824008. https://pubmed.ncbi.nlm.nih.gov/36824008/

1. Che N, Qiu W, Wang JK, Sun XX, Xu LX, Liu R, Gu L. MOTS-c improves osteoporosis by promoting the synthesis of type I collagen in osteoblasts via TGF-β/SMAD signaling pathway. European Review for Medical and Pharmacological Sciences. 2019;23(8):3194-3201. DOI: 10.26355/eurrev_201904_17676. PMID: 31081069. https://pubmed.ncbi.nlm.nih.gov/31081069/

1. 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. Physiological Reports. 2026;14(2):e70791. DOI: 10.14814/phy2.70791. PMID: 41732124. https://pubmed.ncbi.nlm.nih.gov/41732124/

1. 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):5471-5490. DOI: 10.7150/thno.100321. PMID: 39267782. https://pubmed.ncbi.nlm.nih.gov/39267782/

1. Alser M, Ramanjaneya M, Anwardeen NR, Donati F, Botre F, Jerobin J, Bettahi I, Mohamed NA, Abou-Samra AB, Elrayess MA. The Effect of Chronic Endurance Exercise on Serum Levels of MOTS-c and Humanin in Professional Athletes. Reviews in Cardiovascular Medicine. 2022;23(5):181. DOI: 10.31083/j.rcm2305181. PMID: 39077591. https://pubmed.ncbi.nlm.nih.gov/39077591/

Regulatory and Access Sources (FDA)

The legal-status readout is built strictly from the audited FDA sources below. They support the 503A/503B framework, the bulk-substance rules, the compounded-access pathway, and FDA's public calendar naming MOTS-c for evaluation.

1. U.S. Food and Drug Administration. Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. FDA. https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act (verified 2026-05-29).

1. U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks. FDA. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks (verified 2026-05-29).

1. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee. FDA. https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026 (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.

1. U.S. Food and Drug Administration. Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the FD&C Act (guidance landing page). FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/interim-policy-compounding-using-bulk-drug-substances-under-section-503a-federal-food-drug-and (verified 2026-05-29).