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MOTS-C — research-grade lyophilized peptide vial from Peptide.Express, ≥99% HPLC purity
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MOTS-c — Mitochondrial Open Reading Frame of the 12S rRNA Type-C | 16-Amino Acid Mitochondrial-Derived Peptide

Research-Grade Compound

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-C) is a 16-amino-acid peptide encoded within mitochondrial DNA — specifically translated from a short open reading frame in the 12S ribosomal RNA gene, MT-RNR1. Amino acid sequence: MRWQEMGYIFYPRKLR. Molecular formula C101H152N28O22S2, molecular weight 2,174.6 Da, CAS 1627580-64-6.

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MOTS-c mitochondrial peptide research guide →

In-depth research overview, mechanism of action, and study applications.

Showing CoA for 10mg
Certificate Details
Purity≥99%
Methodology
HPLCLC-MS/MS
CAS Number1627580-64-6
Molecular FormulaC101H152N28O22S2
Molecular Weight2174.6 g/mol
SequenceMitochondrial-derived 16-amino-acid peptide (MRP encoded in 12S rRNA)
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This Certificate of Analysis was issued by an independent third-party laboratory. Peptide.Express does not conduct in-house testing. Results are provided as-is from the testing facility and confirm batch identity, purity, and analytical methodology. For questions about specific CoA results, contact [email protected].

≥99% by HPLCLC-MS/MS VerifiedCoA Every BatchIn-Vitro Research Use Only

What is MOTS-c?

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-C) is a 16-amino-acid peptide encoded within mitochondrial DNA — specifically translated from a short open reading frame in the 12S ribosomal RNA gene, MT-RNR1. Amino acid sequence: MRWQEMGYIFYPRKLR. Molecular formula C101H152N28O22S2, molecular weight 2,174.6 Da, CAS 1627580-64-6.

The mitochondrial encoding is what makes it structurally unusual. Virtually every other peptide in biology is transcribed from nuclear DNA and imported where needed. MOTS-c originates inside the organelle and signals outward, which places it in a small class called mitochondrial-derived peptides. It was first characterised in Lee and colleagues' 2015 Cell Metabolism paper.

The "exercise in a vial" framing that follows MOTS-c around is catchy but reductive. What MOTS-c mimics is the metabolic signaling cascade that exercise triggers — AMPK activation and the downstream shift toward fat oxidation and glucose uptake — not exercise itself. The mechanical loading, cardiovascular adaptation and neuromuscular components are untouched. Researchers using the shorthand should be clear about which half of the analogy they mean.

How Does MOTS-c Work? Mechanism of Action

MOTS-c activates AMPK (AMP-activated protein kinase), the cellular energy sensor that redirects metabolism toward glucose uptake and fatty acid oxidation when ATP availability falls. That much is mechanistically solid and replicated across multiple independent preclinical models.

The route to AMPK is the interesting part. Exercise activates AMPK through a shift in the AMP:ATP ratio — a straightforward energy-status signal. MOTS-c activates it through a separate mitochondrial stress pathway involving folate-methionine cycle interference and the resulting accumulation of AICAR, an endogenous AMPK agonist. Two different upstream triggers converging on the same downstream reprogramming.

Under metabolic stress MOTS-c translocates from the mitochondria to the nucleus, where it regulates transcription of genes involved in glucose homeostasis and antioxidant defence. This nuclear translocation separates it from conventional signaling peptides — it acts as a direct transcriptional regulator, not simply as a receptor ligand, and no MOTS-c receptor has been identified.

A third mechanism, mitohormesis, describes the adaptive response to mild mitochondrial stress. Low-grade stress induces protective adaptation that builds resilience against subsequent metabolic challenge. In rodent models this shows up as protection against diet-induced obesity and age-related metabolic decline.

Where the evidence stops: human clinical trial data for MOTS-c remains limited. The mechanistic case from preclinical models is coherent and well replicated, but the translation from rodent metabolic physiology to primate and human physiology has not been demonstrated at the magnitude the preclinical data implies. Study designs should treat the human gap as an open question rather than an assumed extension.

Research Applications of MOTS-c

AMPK and Metabolic Signaling Research

  • AMPK phosphorylation assays: the direct mechanistic readout, measuring Thr172 phosphorylation of the AMPK α-subunit in treated cells.
  • Glucose uptake studies: GLUT4 translocation and radiolabelled glucose uptake as the functional consequence of AMPK activation.
  • Fatty acid β-oxidation: measuring the metabolic shift MOTS-c produces, independently of the upstream AMPK signal.

Mitochondrial-Nuclear Communication

  • Nuclear translocation imaging: tracking MOTS-c movement from mitochondria to nucleus under induced metabolic stress.
  • Retrograde signaling models: MOTS-c is one of the few available tools for studying how mitochondria signal to the nuclear genome rather than the reverse.
  • Antioxidant gene expression: nuclear-regulated transcriptional targets provide a readout distinct from the AMPK arm.

Aging and Exercise Physiology Models

  • Diet-induced obesity models: MOTS-c protection against metabolic decline is among the more replicated preclinical findings.
  • Insulin sensitivity endpoints: glucose tolerance and insulin response in rodent models with and without MOTS-c exposure.
  • Age-dependent physical decline: the Reynolds 2021 Nature Communications work established MOTS-c as exercise-induced and linked it to muscle homeostasis across age.

MOTS-c vs NAD+

FeatureMOTS-cNAD+
Molecular class16-amino-acid peptideDinucleotide coenzyme (not a peptide)
Molecular weight2,174.6 Da663.4 Da
Role in the cellSignaling molecule and transcriptional regulatorSubstrate and electron carrier
Primary mechanismAMPK activation via mitochondrial stress pathwaySirtuin and PARP substrate; ETC electron transport
Genomic originMitochondrial DNA (MT-RNR1)Not gene-encoded — synthesised via salvage and de novo pathways
Reconstituted stability14–28 days at 2–8°C24–48 hours — degrades faster than peptides
Research pairing rationaleAMPK activation raises NAD+ turnoverRestores the substrate pool AMPK signaling depletes

These two are studied together for a specific reason rather than a general one. MOTS-c-driven AMPK activation increases NAMPT expression and raises the rate at which cells consume NAD+ through sirtuin activity. Supplementing NAD+ maintains substrate availability for the pathways MOTS-c is switching on. That substrate-signal pairing is what the Mitochondrial Fuel Stack is built around.

MOTS-c Technical Specifications

Technical specifications for MOTS-c, including molecular data, purity standard, testing methods and storage requirements.
Compound NameMOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-C)
Common SynonymsMOTSc, MOTS-C peptide, mitochondrial-derived peptide MOTS-c
Gene OriginMT-RNR1 (mitochondrial 12S ribosomal RNA gene)
Amino Acid SequenceMRWQEMGYIFYPRKLR
Amino Acid Count16
CAS Number1627580-64-6
Molecular FormulaC101H152N28O22S2
Molecular Weight2,174.6 Da
Purity≥99% by HPLC
Purity ConfirmationLC-MS/MS molecular weight verification
Endotoxin TestingLAL (Limulus Amebocyte Lysate) method
Physical FormLyophilized powder
AppearanceWhite to off-white powder
ReconstitutionBacteriostatic water or sterile 0.9% sodium chloride
Storage (lyophilized)-20°C, desiccated, protected from light
Storage (reconstituted)2–8°C, use within 14–28 days
Shelf Life24 months from manufacture (lyophilized)
Testing MethodsHPLC, LC-MS/MS, LAL Endotoxin
DocumentationCertificate of Analysis (CoA) per batch
WADA StatusProhibited at all times (section S0, non-approved substances)
FDA StatusNot approved for human therapeutic use
Intended UseIn-vitro laboratory research only

How to Reconstitute MOTS-c for Research

MOTS-c contains two methionine residues and a tryptophan — all three are oxidation-prone. Light protection and avoiding repeated freeze-thaw matter more here than they do for a peptide with a more inert residue profile. If a reconstituted MOTS-c solution has been through several thaw cycles, treat the LC-MS/MS identity as no longer guaranteed.

  1. Bring the vial to room temperature before opening.
  2. Draw the calculated volume of bacteriostatic water. For a 10 mg vial, 2 mL yields 5 mg/mL; for the 20 mg vial, 2 mL yields 10 mg/mL; for the 40 mg vial, 4 mL yields 10 mg/mL.
  3. Swab the septum with alcohol and allow 30 seconds to dry.
  4. Inject the diluent slowly against the inner vial wall, not onto the lyophilized cake.
  5. Swirl gently for 60–90 seconds until fully dissolved. Do not shake or vortex.
  6. Confirm a clear, colourless solution with no visible particulate matter.
  7. Label with reconstitution date and concentration, and store protected from light.
  8. Store at 2–8°C and use within 14–28 days. Aliquot if the protocol requires repeated access — the methionine and tryptophan residues make this peptide more sensitive to freeze-thaw than most.

Diluent: bacteriostatic water for peptide reconstitution. Full protocol: step-by-step peptide reconstitution guide. Concentration maths: peptide reconstitution calculator.

Frequently Asked Questions — MOTS-c

What is MOTS-c peptide?

MOTS-c is a 16-amino-acid peptide encoded within mitochondrial DNA, translated from a short open reading frame in the 12S ribosomal RNA gene (MT-RNR1). Sequence MRWQEMGYIFYPRKLR, molecular weight 2,174.6 Da. It belongs to a small class called mitochondrial-derived peptides and is studied for its activation of the AMPK metabolic pathway.

What is the MOTS-c amino acid sequence?

MRWQEMGYIFYPRKLR — sixteen residues: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg. Molecular formula C101H152N28O22S2, molecular weight 2,174.6 Da.

How does MOTS-c differ from other peptides?

By where it comes from. Almost every peptide in biology is encoded in nuclear DNA. MOTS-c is encoded in mitochondrial DNA and signals outward from the organelle — it even translocates to the nucleus under metabolic stress and regulates gene transcription directly. That makes it a mitochondrial-to-nuclear messenger rather than a conventional receptor ligand, and no MOTS-c receptor has been identified.

Is MOTS-c really "exercise in a vial"?

Partly, and the shorthand does more harm than good. MOTS-c activates AMPK, which is one of the signaling cascades exercise triggers, and the downstream metabolic reprogramming does overlap. It does nothing about mechanical loading, cardiovascular adaptation, or neuromuscular recruitment. It mimics one signaling arm of exercise, not exercise.

What is AMPK and why does MOTS-c activate it?

AMPK is AMP-activated protein kinase, the cellular energy sensor that switches metabolism toward glucose uptake and fatty acid oxidation when ATP falls. MOTS-c reaches it through a mitochondrial stress pathway involving folate-methionine cycle interference and AICAR accumulation — a different upstream trigger than the AMP:ATP shift that exercise produces, converging on the same downstream response.

What is the difference between MOTS-c and NAD+?

MOTS-c is a 16-residue peptide that acts as a signal. NAD+ is a 663.4 Da dinucleotide coenzyme that acts as a substrate — it carries electrons in the transport chain and is consumed by sirtuins and PARP enzymes. One switches pathways on; the other is the fuel those pathways run through. They are studied together because AMPK activation raises NAD+ consumption.

Can MOTS-c and NAD+ be studied together?

Yes, and there is a specific rationale for it. MOTS-c-driven AMPK activation upregulates NAMPT, the rate-limiting enzyme of the NAD+ salvage pathway, while simultaneously increasing metabolic activity that consumes NAD+. Supplementing NAD+ maintains substrate availability. Peptide.Express supplies both together as the Mitochondrial Fuel Stack.

Does MOTS-c affect insulin sensitivity in research models?

In rodent models, yes — MOTS-c administration improves insulin sensitivity and protects against diet-induced obesity, findings established in the 2015 Cell Metabolism work and replicated since. Whether that translates to primate or human physiology at comparable magnitude has not been demonstrated. The human trial data is limited.

Is MOTS-c WADA prohibited?

Yes, at all times, under section S0 of the Prohibited List covering non-approved substances. It is not FDA-approved for any human indication.

What is MOTS-c's role in aging research?

Circulating MOTS-c declines with age, and the Reynolds 2021 Nature Communications work established it as exercise-induced and connected to muscle homeostasis across the lifespan. The mitohormesis mechanism — mild mitochondrial stress producing adaptive resilience — is the specific hypothesis being tested. As with the metabolic findings, the preclinical case is stronger than the human evidence.

What purity standard does Peptide.Express use for MOTS-c?

≥99% by reverse-phase HPLC, with LC-MS/MS confirming the 2,174.6 Da mass. Mass confirmation is worth checking on the CoA — MOTS-c is sometimes confused with humanin and other mitochondrial-derived peptides, which have different masses entirely.

What testing does MOTS-c undergo before shipping?

Reverse-phase HPLC for purity by area under curve, LC-MS/MS for molecular weight identity confirmation, LAL endotoxin testing, and visual QC. All performed by an independent third-party laboratory with a batch-specific Certificate of Analysis.

How should MOTS-c be stored before and after reconstitution?

Lyophilized at -20°C, desiccated and protected from light, stable for 24 months. Reconstituted at 2–8°C for 14–28 days. Aliquot before freezing if repeated access is needed — the two methionine residues and the tryptophan are oxidation-prone, which makes this peptide more freeze-thaw sensitive than most.

How do I reconstitute MOTS-c?

Add bacteriostatic water slowly against the inner vial wall. For a 10 mg vial, 2 mL yields 5 mg/mL. Swirl for 60–90 seconds without shaking, confirm the solution is clear and colourless, then store at 2–8°C protected from light.

Where is the Certificate of Analysis for MOTS-c?

On this page and in the Peptide.Express lab results library. Each CoA is batch-specific and lists HPLC purity, LC-MS/MS mass confirmation, endotoxin result, testing laboratory and test date.

Research References

  1. Lee C, Zeng J, Drew BG, et al. "The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance." Cell Metabolism, 2015. Read the Lee 2015 Cell Metabolism MOTS-c paper
  2. Reynolds JC, Lai RW, Woodhead JST, et al. "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis." Nature Communications, 2021. Read the Reynolds 2021 Nature Communications MOTS-c paper
  3. Review of MOTS-c as a mitochondrial-derived peptide with therapeutic research applications, covering the AMPK mechanism and current evidence limits. Frontiers in Endocrinology. Read the MOTS-c mitochondrial-derived peptide review on PMC
  4. USADA reference page on MOTS-c covering its prohibited status and the anti-doping context for mitochondrial-derived peptides. Read the USADA reference on MOTS-c prohibited status

All products are sold for in-vitro laboratory research use only. Not intended for human consumption, clinical use, or veterinary use. Peptide.Express makes no medical claims. Consult the published literature for research application guidance.

Further Reading

Related Research Compounds

NAD+The substrate pool that MOTS-c-driven AMPK activation draws down.Mitochondrial Fuel StackMOTS-c and NAD+ supplied together for substrate-signal pairing studies.SS-31Cardiolipin-binding peptide addressing mitochondrial structure rather than metabolic signaling.EpithalonAEDG tetrapeptide studied in the adjacent cellular-senescence research area.