Source: https://peakpeptides.com/peptides/mots-c/ Peptide library · Mitochondrial peptide # MOTS-c A 16-amino-acid signaling peptide encoded within mitochondrial DNA. Most findings come from cultured cells and mice; human research measures naturally circulating MOTS-c rather than testing it as a medicine. Last reviewed September 22, 2026 At a glance - **Also called:** Mitochondrial-derived peptide MOTS-c; MT-RNR1-encoded peptide - **What it is:** A mitochondrial 16-amino-acid peptide - **Evidence:** Mostly cells and mice; observational human data - **FDA status:** Not FDA-approved for any use - **In sport:** Prohibited by WADA under S4.4.1[10] - **At Promise Peptides:** Listed; currently waitlist-only The short version MOTS-c is a short peptide made from instructions inside mitochondrial DNA. Researchers study it as a signal between mitochondrial metabolism and the rest of the cell. Experiments in cells and mice cover metabolism, stress responses and physical function. Human work is mainly observational: it measures the body’s own MOTS-c and looks for associations. MOTS-c is not FDA-approved. Its compounding nomination was withdrawn, but FDA’s published safety note remains, and human interventional safety and effectiveness are not established. Any prescription decision belongs with a licensed provider. ## What it is MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c. Unlike most peptides, whose instructions are in nuclear DNA, MOTS-c is encoded within the mitochondrial 12S ribosomal RNA gene, MT-RNR1. It is detectable in human plasma and skeletal muscle. The peptide is endogenous, meaning the human body can make it, but a lab-made preparation is an external substance. MOTS-c contains 16 amino acids with the sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg. The cited discovery paper supports the sequence.[1] ## Where the research stands The foundational work is preclinical. It describes metabolic signaling in cultured cells and mouse models, including how MOTS-c can move into the nucleus during cellular stress. The human studies cited here measured naturally occurring MOTS-c; they did not test it as a treatment. How far the evidence has climbed 1. Cell studies · Yes · Human and mouse cells under metabolic stress 2. Animal studies · Yes · Metabolic and muscle research in mice 3. Small human pilots · Limited · Observational biomarker studies only 4. Controlled human trials · None · No human efficacy trial identified in the cited research 5. FDA approval · No · Not approved for any use Here is what some of the most-cited studies looked at. Each names its species, because a result in a mouse is not a result in a person. - **The founding metabolism study** (Mice · Cells · 2015): Researchers identified the mitochondrial sequence and studied folate-cycle, purine and AMPK signaling in cultured cells. In mice, they measured responses to a high-fat diet. These were not human treatment findings.[1] - **Movement into the nucleus** (Human and mouse cells · 2018): The study measured movement into the nucleus and stress-response gene expression in cultured human and mouse cells under metabolic stress. It did not test a treatment in people.[2] - **Exercise and aging models** (Humans · Mice · 2021): In humans, the study measured endogenous MOTS-c expression in skeletal muscle and circulation after exercise. Separate mouse experiments measured running, grip and gait after exogenous MOTS-c; they did not test a human treatment.[3] - **Stress and metabolism review** (Review · 2023): A review integrated the cell, animal and human biomarker literature and emphasized the peptide’s proposed signaling roles. It did not identify controlled human treatment evidence.[4] - **A proposed direct target** (Mice · Cell-free · 2024): Cell-free assays measured binding to casein kinase 2, while mouse experiments examined muscle glucose uptake and disuse-related muscle changes. The work did not test a human treatment.[5] - **The human reports** (Humans · 2024): A prospective cohort measured circulating MOTS-c in 94 people receiving chronic hemodialysis and tested its association with later clinical events. Because it was observational, it cannot show that giving MOTS-c changes risk.[6] ## What the research can’t tell you - **No human treatment trial**: The cited research does not include a controlled human treatment trial of MOTS-c. Biomarker associations cannot answer that question.[6] - **Mouse results stay in mice**: Metabolic and muscle treatment findings came from mouse models. The human exercise finding concerned endogenous MOTS-c, not administration as a treatment.[3][5] - **Human handling is unknown**: The cited research does not establish human half-life, bioavailability or exposure-response relationships. Animal protocols cannot fill that gap. - **Sport rules add another limit**: MOTS-c is prohibited under WADA’s anti-doping rules. Anti-doping rules are separate from FDA approval and clinical decisions.[10] ## FDA status Not FDA-approved for any use FDA’s page, content current as of April 22, 2026, lists MOTS-c under “nominated but withdrawn” while retaining the published safety note. Withdrawal does not change the other requirements that apply to compounding.[7] MOTS-c is not on FDA’s finalized list of additional bulk substances for patient-specific compounding.[8] Before a July 2026 advisory meeting, FDA staff proposed against adding it; FDA had posted no official vote record as of September 17, 2026.[9] Promise Peptides is currently taking waitlist sign-ups. Joining is not a medical request and no prescription comes from it. ## A prescription route Promise is currently accepting waitlist signups. Joining is not a treatment request and does not result in a prescription. If treatment visits open, any treatment request would require clinical review; prescribing and pharmacy fulfillment would remain separate decisions. 1. **Start on Promise’s MOTS-c page**: It shows what the treatment involves and its current availability. 2. **Answer the MOTS-c questionnaire**: A licensed provider reviews health history, medicines and goals, and can decline. Not everyone qualifies. 3. **Pharmacy review is a separate step**: A prescription does not guarantee preparation or dispensing. A pharmacy must separately determine whether it can fulfill the prescription under the applicable requirements. A prescription does not make MOTS-c FDA-approved or turn mouse experiments into human evidence; it means a clinician reviewed the individual case. MOTS-c at Promise Read the treatment information and view the current waitlist. [Join the Promise waitlist](https://mypromise.com/products/mots-c?utm_source=peak&utm_medium=affiliate&utm_campaign=library&utm_content=mots-c) Peak may earn money when readers become Promise patients. Joining does not guarantee future treatment availability. Availability would depend on the treatment, state, clinical review and separate pharmacy review. ## Questions ### What is MOTS-c? It is a 16-amino-acid peptide encoded within mitochondrial DNA. The body makes endogenous MOTS-c, while research preparations are synthesized outside the body.[1] ### Has MOTS-c been tested as a medicine in people? No controlled human treatment trial is identified in the sources cited here. Human work measures natural MOTS-c rather than administering it.[6] ### Is MOTS-c FDA-approved? No. Its compounding nomination appears in FDA’s withdrawn table, and it is not on the finalized federal bulk-substance list.[7][8] ## Sources 1. Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. *Cell Metab*. 2015;21:443-454. [PubMed 25738459](https://pubmed.ncbi.nlm.nih.gov/25738459/) 2. Kim KH, et al. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. *Cell Metab*. 2018;28:516-524.e7. [PubMed 29983246](https://pubmed.ncbi.nlm.nih.gov/29983246/) 3. Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. *Nat Commun*. 2021;12:470. [PubMed 33473109](https://pubmed.ncbi.nlm.nih.gov/33473109/) 4. Wan W, et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. *J Transl Med*. 2023;21:36. [PubMed 36670507](https://pubmed.ncbi.nlm.nih.gov/36670507/) 5. Kumagai H, et al. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. *iScience*. 2024;27:111212. [PubMed 39559755](https://pubmed.ncbi.nlm.nih.gov/39559755/) 6. Bolignano D, et al. The mitochondrial-derived peptide MOTS-c may refine mortality and cardiovascular risk prediction in chronic hemodialysis patients. *Blood Purif*. 2024;53:824-837. [PubMed 39111290](https://pubmed.ncbi.nlm.nih.gov/39111290/) 7. U.S. Food and Drug Administration. [Certain bulk drug substances for use in compounding that may present significant safety risks](https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks). Content current as of April 22, 2026. 8. U.S. Food and Drug Administration. [Bulk drug substances used in compounding under section 503A of the FD&C Act](https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act). 9. U.S. Food and Drug Administration. [July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee](https://www.fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-compounding-advisory-committee-07232026). 10. World Anti-Doping Agency. [The 2026 Prohibited List](https://www.wada-ama.org/en/prohibited-list) (S4.4.1). ## Also in the library - [NAD+](https://peakpeptides.com/peptides/nad-plus/) (Coenzyme) - [Sermorelin](https://peakpeptides.com/peptides/sermorelin/) (Growth hormone) - [Semaglutide](https://peakpeptides.com/peptides/semaglutide/) (Metabolic) - [Tirzepatide](https://peakpeptides.com/peptides/tirzepatide/) (Metabolic) --- Peak maps the terrain; it does not examine anyone, so nothing here is medical advice, and the decision about any treatment belongs to a licensed provider who has reviewed your health. Peak may earn money when readers become Promise patients. Peak is not affiliated with any company called Peak Peptides or Peak Performance Peptides.