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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 October 8, 2026

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 Its compounding nomination was withdrawn, but FDA’s published safety note remains, and human interventional safety and effectiveness are not established.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 studiesYesHuman and mouse cells under metabolic stress
  2. Animal studiesYesMetabolic and muscle research in mice
  3. Small human pilotsLimitedObservational biomarker studies only
  4. Controlled human trialsNoneNo human efficacy trial identified in the cited research
  5. FDA approvalNoNot 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.

  • MiceCells2015

    The founding metabolism study

    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

  • Human and mouse cells2018

    Movement into the nucleus

    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

  • HumansMice2021

    Exercise and aging models

    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

  • Review2023

    Stress and metabolism review

    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

  • MiceCell-free2024

    A proposed direct target

    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

  • Humans2024

    The human reports

    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.35

  • 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 prescribes MOTS-c now through licensed U.S. providers. A provider reviews every request and decides; not everyone qualifies.

A prescription route

Promise prescribes MOTS-c now. Here is the route to a licensed U.S. provider’s review; not everyone qualifies:

  1. Start on Promise’s MOTS-c page

    The page has a visit-start link and a price. A request does not guarantee a prescription.

  2. Share your health information

    A licensed U.S. provider reviews every request, including 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 licensed U.S. compounding pharmacy must review whether it can fulfill the prescription under the applicable requirements. Compounded medications are not FDA-approved.

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

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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.78

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
  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
  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
  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
  5. Kumagai H, et al. MOTS-c modulates skeletal muscle function by directly binding and activating CK2. iScience. 2024;27:111212. PubMed 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
  7. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that 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.
  9. U.S. Food and Drug Administration. July 23-24, 2026: Meeting of the Pharmacy Compounding Advisory Committee.
  10. World Anti-Doping Agency. The 2026 Prohibited List (S4.4.1).