Overview
A 16-amino-acid mitochondrial-derived peptide encoded in mitochondrial DNA. Research interest centres on metabolic regulation, exercise physiology and biological ageing.
Mechanism of Action
MOTS-c is encoded within the mitochondrial 12S rRNA gene, making it one of a small family of mitochondrial-derived peptides rather than a nuclear gene product.
Published work reports activation of the AMPK pathway, a central cellular energy sensor associated with glucose uptake and fatty-acid oxidation.
The peptide is described as translocating to the nucleus under metabolic stress, where it influences transcription of antioxidant and metabolic stress-response genes.
Effects on the folate–methionine cycle and on de novo purine biosynthesis are reported as an upstream contributor to AMPK activation.
Areas Being Studied
- Insulin sensitivity and glucose metabolism
- Exercise capacity and physical performance
- Biological ageing and mitochondrial function
- Diet-induced obesity models
Listing a research area does not imply efficacy, approval, or suitability for any use.
Research Summary
- The identifying paper described MOTS-c as a regulator of insulin sensitivity and metabolic homeostasis in mice, with protection against diet-induced obesity reported.
- Later work reported that circulating MOTS-c levels rise with exercise in humans and that administration improved physical capacity in aged mice.
- A specific mitochondrial DNA polymorphism affecting the MOTS-c sequence has been associated in population research with differences in metabolic risk.
- Human interventional trial data remains limited; most of the evidence base is cellular and animal work.
Potential Adverse Effects Reported in Research
- Reported animal studies describe few adverse observations at the doses studied.
- Human safety data is not established; no large clinical safety dataset has been published.
- Injection-site reactions are the most common practical observation reported.
- Because AMPK activation influences glucose handling, researchers note the mechanism overlaps with metabolic pathways of interest in glycaemic research.
Reconstitution Basics
Usually supplied as 5 mg or 10 mg lyophilised powder. Doses in research protocols are commonly in the low milligram range.
Bacteriostatic water
Sterile water containing roughly 0.9% benzyl alcohol as a preservative, which inhibits bacterial growth in multi-access vials.
Sterile technique
Laboratory documentation describes disinfecting the stopper, using a fresh sterile needle for each access, and avoiding contact with non-sterile surfaces.
After reconstitution
Solutions are refrigerated, protected from light, and not subjected to repeated freeze–thaw cycles.
This section is educational background on laboratory handling. It is not an instruction or protocol.
Open the reconstitution calculator →Dosing & Reconstitution Guide
Documented MOTS-C protocols use a 40 mg vial reconstituted with 3.0 mL of bacteriostatic water, giving ~13.33 mg/mL (13,333 mcg/mL), so 1 unit on a U-100 syringe ≈ 133.3 mcg. Referenced schedules are once-daily subcutaneous, titrated from ~200 mcg to ~1,000 mcg per day in roughly 200 mcg steps over an ~10-week course. MOTS-C is an unapproved research chemical with no completed human efficacy trials.
Protocol overview
- Reconstitution: 3.0 mL bacteriostatic water per 40 mg vial → ~13.33 mg/mL; 1 unit ≈ 133.3 mcg on a U-100 syringe.
- One subcutaneous injection each day, holding each dose level about two weeks before stepping up as tolerated.
- The 200 mcg starting step is only ~1.5 units, so syringe resolution — not the peptide — is the limiting factor at the bottom of the ladder. Filling the same vial with 4.0 mL instead (10 mg/mL) would make 100 mcg exactly 1 unit and shift the ladder to 2–10 units, if the vial accepts that volume.
- Vial planning at the lower titration doses: roughly 1 vial for 8 weeks, 2 for 12 weeks, 3 for 16 weeks.
- Supplies for once-daily dosing: ~56 U-100 syringes and ~112 alcohol swabs per 8 weeks.
- Figures come from commonly cited reference protocols and animal-to-human extrapolation, not from approved human dosing.
Dosing protocol — standard titration
| Phase | Reported dose | Notes |
|---|---|---|
| Weeks 1–2 | 200 mcg once daily~1.5 units (0.015 mL) at ~13.33 mg/mL. | ~1.5 units (0.015 mL) at ~13.33 mg/mL. |
| Weeks 3–4 | 400 mcg once daily~3 units (0.03 mL). | ~3 units (0.03 mL). |
| Weeks 5–6 | 600 mcg once daily~4.5 units (0.045 mL). | ~4.5 units (0.045 mL). |
| Weeks 7–8 | 800 mcg once daily~6 units (0.06 mL). | ~6 units (0.06 mL). |
| Weeks 9–10+ | 1,000 mcg once daily~7.5 units (0.075 mL) upper end of the cited ladder. | ~7.5 units (0.075 mL) upper end of the cited ladder. |
Dosing protocol — gradual titration
| Phase | Reported dose | Notes |
|---|---|---|
| Weeks 1–3 | 200 mcg once daily~1.5 units. Longer hold at the entry step. | ~1.5 units. Longer hold at the entry step. |
| Weeks 4–6 | 400 mcg once daily~3 units. | ~3 units. |
| Weeks 7–9 | 600 mcg once daily~4.5 units. | ~4.5 units. |
| Weeks 10–12 | 800 mcg once daily~6 units held as the maintenance range. | ~6 units held as the maintenance range. |
| After the course | Off-cycleCited courses are cycled, not continuous. | Cited courses are cycled, not continuous. |
Schedules summarise what appears in published studies, trial protocols or manufacturer documentation. They are reference material, not a recommendation.
Where to Buy Compounds & Supplies
External link. PepDex does not sell products and does not endorse any supplier.
Supplies needed
Lyophilised peptide vial
Sealed vial with an intact stopper and a legible mass label (mg or mcg).
Bacteriostatic water
Sterile water with ~0.9% benzyl alcohol, used where a vial will be accessed more than once. Sterile water for injection is used for single-access work.
Reconstitution syringe
A 1–3 mL syringe with a larger-gauge needle for drawing and transferring solvent.
Insulin syringe (U-100)
Fine-gauge syringe graduated in units; 100 units = 1 mL. Used for accurate small-volume measurement.
Alcohol prep pads
70% isopropyl swabs for disinfecting both vial stoppers before every access.
Sharps container
Rigid, puncture-resistant container for single-use needle disposal.
Refrigeration and light protection
2–8 °C storage plus an opaque box or the original carton for reconstituted vials.
Labels
Date of reconstitution, resulting concentration and compound name on every vial.
Reconstitution steps
- 01
Bring the vial to room temperature
Lyophilised powder is allowed to equilibrate out of the refrigerator before the stopper is pierced, which reduces condensation inside the vial.
- 02
Disinfect both stoppers
The peptide vial and the bacteriostatic water vial are each swabbed with 70% isopropyl alcohol and allowed to air dry.
- 03
Draw the calculated solvent volume
Solvent volume is chosen to produce a convenient concentration — the reconstitution calculator converts vial mass and solvent volume into concentration and syringe units.
- 04
Add the solvent slowly down the vial wall
The stream is directed against the glass rather than onto the powder cake. Peptides are shear-sensitive and direct jetting is avoided.
- 05
Dissolve without shaking
The vial is left to stand, then gently swirled or rolled. Shaking introduces foam and mechanical stress that can denature peptide chains.
- 06
Inspect the solution
Documentation describes checking for a clear, particle-free solution. Cloudiness, visible particulate or discolouration is treated as a failed preparation.
- 07
Label and refrigerate
The vial is labelled with compound, concentration and date, then stored at 2–8 °C protected from light.
Storage instructions
- Lyophilised: store the dry vial at −20 °C (−4 °F), dry and protected from light.
- Reconstituted: refrigerate at 2–8 °C (35.6–46.4 °F) and use within about 7 days.
- Do not freeze the reconstituted solution — freeze–thaw cycles can denature the peptide.
- Add the bacteriostatic water slowly down the inner vial wall to limit foaming, and swirl rather than shake.
- Label each vial with the reconstitution date and resulting concentration.
Half-Life
~30 minutes to a few hours
Circulating half-life is short in reported measurements; study designs typically use frequent or cyclical administration.
Storage
- Before reconstitution
- Lyophilised powder stored frozen for long-term stability.
- After reconstitution
- Refrigerated at 2–8 °C after reconstitution.
- Light protection
- Protected from light and repeated temperature cycling.
- Shelf-life considerations
- Shorter usable window than long-acting peptides; typically described in weeks.
Frequently Asked Questions
References
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Educational reference only. Figures are compiled from published research literature. PepDex does not provide medical advice, dosing recommendations, or instructions for use.