MOTS-c: the basics
What is it?
A small peptide associated with mitochondria, the parts of cells that help produce energy. Researchers study its role in metabolism and exercise.
Original study ↗What do people claim it helps with?
More energy, improved fitness, better blood-sugar control and slower aging. These treatment claims are not established in people.
What has research actually shown?
Giving MOTS-c to mice affected metabolism and physical performance. Human exercise studies measured naturally occurring MOTS-c; they did not prove that taking it produces the same benefits.
Original study ↗Has this been demonstrated in people?
Treatment findings are predominantly laboratory and animal research. Measuring a hormone in people after exercise is not a trial of administering that hormone.
Original study ↗What side effects, risks and unknowns should I understand?
Human treatment safety, interactions and long-term effects remain unknown. FDA reports no identified human exposure data for administered MOTS-c.
FDA safety information ↗Is it an approved medicine?
No FDA-approved medicine contains this peptide. Availability online or through a clinic does not mean it has been approved.
FDA safety information ↗Approval here means U.S. FDA approval and applies to a particular product, formulation and use. This is a starting overview, not a complete side-effect list. Sources checked 10 October 2026; independent scientific review pending.
How is it used or studied?
Studied using specific research preparations. There is no FDA-approved treatment formulation; an online vial, capsule or spray is not necessarily the product used in a study.
Different routes and formulations can have different effects. A study of one product does not validate every product with the same peptide name.
A common misunderstanding
Trials of a modified drug candidate are not automatically trials of native MOTS-c.
What should I ask a clinician?
- What diagnosis or goal are we trying to address, and what established options are available?
- Was the expected benefit shown in people like me, using this exact product?
- How could my medicines, health conditions or pregnancy plans affect the risks?
- What monitoring is needed, and what would tell us the treatment is helping or should be stopped?
What do the research words mean?
- Peptide
- A short chain of amino acids, the building blocks of proteins.
- Preclinical
- Research in cells, tissues or animals before dependable treatment evidence in people.
- Controlled trial
- A study comparing a treatment with another treatment or a placebo to help separate its effects from other explanations.
- Biomarker
- A measurement, such as a hormone level. A change does not necessarily mean someone feels better or lives longer.
MOTS-c Evidence & Clinical Profile
Human Study Limits
MOTS-c has been investigated in clinical contexts. Patient outcomes must be evaluated against study size, design, and control cohorts.
Laboratory & In Vivo Assays
Cellular and animal disease models examine receptor binding affinities and signaling cascades, which require human confirmation.
What is MOTS-c?
Mitochondrial ORF of the 12S rRNA type-c is A 16-amino-acid peptide encoded within the mitochondrial 12S ribosomal RNA genome. Shown in rodent studies to activate AMPK and improve muscle insulin sensitivity, but completely lacks human therapeutic efficacy trials. Aliases include: Mitochondrial-derived peptide, MDP MOTS-c.
- Sequence (one-letter)
- MRWQEMGYIFYPRKLR
- Molecular formula
- C101H152N28O22S2
- Molecular weight
- 2174.6 g/mol
- CAS Number
- 1627580-64-6
- UNII Code
- A5CV6JFB78
- PubChem CID
- 146675088
Identifiers checked against PubChem and FDA's Global Substance Registration System on 13 October 2026. FDA substance record ↗ · PubChem record ↗ See all names and codes in the peptide name index.
Clinical Trials & Human Cohorts
Human research can examine tolerability, symptoms or patient outcomes. The design and comparator determine what each result can establish.
Endogenous MOTS-c Responses to Acute High-Intensity Exercise [1]
What was reported
Exercise induced endogenous MOTS-c expression in skeletal muscle and in circulation.
What limits the conclusion
Small observational biomarker measurement; MOTS-c was not given to people, so it says nothing about treatment effects.
How the compound may work
Mechanisms describe how MOTS-c may affect biological processes. Laboratory findings and patient outcomes answer different questions.
AMPK Phosphorylation via AICAR Pathway
Inhibits folate metabolism to induce AICAR accumulation, activating AMP-activated protein kinase (AMPK). [2]
Nuclear Translocation Under Stress
Translocates to the nucleus during metabolic stress in an AMPK-dependent manner and regulates nuclear genes, including those with antioxidant response elements. [3]
Areas Being Studied
These research topics reflect active areas of scientific exploration, distinct from unverified commercial marketing claims.
Insulin Resistance & Diet-Induced Obesity
Prevention of weight gain and glucose tolerance improvement on high-fat diet. [2]
Exercise Mimicry & Physical Capacity
Improved physical performance in young, middle-aged and old mice, including after late-life intermittent treatment. [1]
Compare the study designs.
| Study | Design / sample | Outcome type | Key limitation |
|---|---|---|---|
| Exercise Biomarker Cohort · 2021 [1] | Human exercise sub-study within a mostly mouse paper n = 10 |
Clinical endpoint evaluation | Small observational biomarker measurement; MOTS-c was not given to people, so it says nothing about treatment effects. |
Regulatory Status & Clinical Safety
Regulatory Classification
Unapproved research substance. Named on the 2026 WADA Prohibited List under S4.4.1 (metabolic modulators: activators of AMP-activated protein kinase), prohibited at all times.
Safety Realities & Impurities
Safety depends on the molecule, formulation, route and evidence. A laboratory purity measurement alone cannot establish safety for human use.
Clinical Trials Registry Records
Official registry records from ClinicalTrials.gov. Study registration does not imply government endorsement or guaranteed efficacy.
WADA & Anti-Doping Regulations
WADA Section S4: Prohibited Substance
The World Anti-Doping Agency (WADA) classifies MOTS-c under Section S4 of the Prohibited List. Prohibited at all times (in- and out-of-competition). Last verified: October 2026.
Research Timeline
-
2015
Discovery
Lee and colleagues discover MOTS-c encoded in mitochondrial 12S rRNA. [2]
-
2021
Exercise Cohort
Mouse physical-capacity data and a small human exercise biomarker sub-study published. [1]
-
2026
WADA S4 Listing
Named as an AMPK activator under S4.4.1 (metabolic modulators); prohibited at all times. [4]
What Researchers Still Don't Know
Long-term safety profiles
Multi-year observational data in broader heterogeneous cohorts remains uncharacterized.
Optimal dose-response thresholds
Comparative trials optimizing minimal effective exposure versus adverse event rates.
Formulation bioavailability
Differences between oral, subcutaneous, and modified peptide delivery vehicles.
References
Primary sources verified against PubMed / NLM and regulatory databases.
- Biomarker Study
-
Primary Discovery
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis ↗ (external website)
- Mechanistic Study
- Anti-Doping