Overview
In plain English
MOTS-C is unusual: it is encoded by mitochondrial DNA — within the 12S rRNA gene — rather than by the nuclear genome, which places it in the small class of mitochondrial-derived peptides.
It is studied in published research for AMPK-dependent metabolic signalling, insulin-independent glucose uptake in skeletal muscle, and mitochondrial-to-nuclear stress signalling. Endogenous levels rise with exercise and fall with age, which is the basis of most of the research interest. Strictly for laboratory research use. Not for human or veterinary consumption.
- What it isA 16-amino-acid peptide encoded by mitochondrial DNA
- Mainly studied forAMPK signalling, glucose handling in muscle models, and mitochondrial retrograde signalling
- Supplied asLyophilised powder, 10mg and 40mg vials, independently assayed
How it works
What it actually does
Cells have a master switch — AMPK — that shifts them from storing energy to using it. MOTS-C is reported to turn that switch on.
It does so indirectly. Rather than binding a receptor, it restricts flux through the folate–methionine cycle so that AICAR, an endogenous activator, accumulates inside the cell — and AICAR activates AMPK.
Downstream, mouse studies reported more glucose taken up by skeletal muscle without additional insulin, increased fatty acid oxidation, and resistance to diet-induced adiposity.
The science in detail
MOTS-C belongs to a small class of mitochondrial-derived peptides — short open reading frames encoded within mitochondrial ribosomal RNA genes rather than nuclear DNA. Humanin and the SHLP series arise from the 16S rRNA gene; MOTS-C from the 12S. Lee et al. (Cell Metabolism, 2015) identified the peptide, showed it circulates, and characterised its metabolic activity.
Its mechanism is indirect and unusual. Rather than binding a cell-surface receptor, MOTS-C acts on the folate-methionine one-carbon cycle, suppressing flux through de novo purine biosynthesis. The consequence is accumulation of AICAR — 5-aminoimidazole-4-carboxamide ribonucleotide — an endogenous intermediate that allosterically activates AMP-activated protein kinase. AMPK activation is therefore downstream of a metabolite shift rather than of direct binding, which separates MOTS-C from biguanides such as metformin, which raise the AMP:ATP ratio by inhibiting respiratory complex I, and from direct AMPK agonists.
Once AMPK is engaged the profile is conventional catabolic signalling: increased GLUT4 translocation and insulin-independent glucose uptake in skeletal muscle, increased fatty acid oxidation, and suppression of lipogenic and gluconeogenic programmes. In the original mouse work this presented as resistance to diet-induced adiposity and improved insulin sensitivity.
MOTS-C also has a nuclear role. Kim et al. (Cell Metabolism, 2018) reported that under metabolic stress the peptide translocates to the nucleus, associates with stress-responsive transcription factors and regulates antioxidant response element-driven genes. That gives it a retrograde signalling function — mitochondria issuing adaptive instructions to the nuclear genome — and it is the feature drawing most current research attention.
Reynolds et al. (Nature Communications, 2021) characterised MOTS-C as exercise-responsive: circulating and skeletal muscle levels rise with exercise in humans, and administration to aged mice improved measures of physical capacity and muscle homeostasis. That work underlies its description as an exercise-mimetic in the literature. Endogenous levels decline with age, and a mitochondrial DNA variant altering the peptide sequence has been examined in relation to longevity in East Asian cohorts.
Evidence
What the research shows
Made by mitochondria
One of a small group of peptides encoded in mitochondrial DNA rather than the nuclear genome.
Activates the cell's energy switch
It activates AMPK — the master regulator that shifts cells from storing fuel to using it.
Improved glucose handling in mouse models
The original work reported better insulin sensitivity and resistance to diet-induced adiposity in mice.
Rises with exercise in humans
Circulating levels increase with exercise; aged mice given it showed improved physical capacity.
Reconstitution & handling
Reconstitution and handling in the laboratory
These are general handling notes for the lyophilised peptide supplied by Purist Peptides. They describe the preparation of a stock solution for laboratory work. They are not a dosing protocol, and they describe no administration to a person or an animal.
A 3ml vial of bacteriostatic water is included free with every peptide vial you order, so the material can be reconstituted on arrival.
MOTS-C 10mg and 40mg — preparing a stock solution
Choice of diluent
Bacteriostatic water (water for injection with 0.9% benzyl alcohol) is the usual diluent where a stock will be drawn from repeatedly, because the preservative permits several septum entries across a working period. Sterile water for injection and sterile 0.9% sodium chloride are both used where a single-use preparation is wanted instead. The diluent volume sets the concentration of the stock, so record it.
Sterile technique
- Allow the sealed vial to reach room temperature before opening the carton — reconstituting a cold lyophilised cake slows dissolution
- Work in a clean area or a laminar flow cabinet, and wipe the rubber septum with 70% isopropyl alcohol, letting it dry fully
- Draw the chosen volume of diluent using a sterile single-use syringe and needle
- Angle the needle so the diluent runs down the inside wall of the vial — do not direct the stream onto the lyophilised cake
- Roll the vial gently between the palms until the cake has dissolved completely. Do not shake and do not vortex: peptides are surface-active, and agitation drives foaming and aggregation
- Let the vial stand for 5 to 10 minutes. A correctly reconstituted solution is clear and free of visible particles
Working out the concentration
Concentration follows from the mass in the vial and the volume of diluent added, nothing else. Adding 1ml of diluent to the 10mg vial gives a 10mg/ml stock; adding 2ml to the 40mg vial gives 20mg/ml. Label every reconstituted vial with its concentration and the date it was prepared.
Storage and stability
Before reconstitution
The lyophilised powder is the stable form. Sealed vials are best held at −20°C, protected from light and from moisture; the short periods at 2 to 6°C that occur in transit and on arrival are expected and are accounted for in the supply chain. Keep the vial in its carton — light and humid air are the two ordinary causes of loss on storage.
After reconstitution
Hold reconstituted solution at 2 to 6°C and protect it from light. Do not freeze a working stock: freeze-thaw cycling is the main avoidable cause of degradation and of visible precipitate. Where material must be held beyond a short working period, aliquot the stock into sterile low-binding tubes and freeze the aliquots once at −20°C or below, thawing each aliquot only once.
Checks before use
Inspect every vial against a light source. Discard any solution that is hazy, discoloured or contains particles, and any vial whose septum integrity is in doubt. The independent HPLC assay report for the batch supplied is available on request.
Strictly for laboratory research use. Not for human or veterinary consumption.
Questions
Frequently asked questions
What makes MOTS-C different from other peptides?
Its origin. Almost all research peptides are fragments or analogues of nuclear-encoded proteins. MOTS-C is transcribed from mitochondrial DNA, within the 12S rRNA gene, which places it in the small class of mitochondrial-derived peptides alongside humanin and the SHLPs.
Does MOTS-C bind a receptor?
No specific cell-surface receptor has been established. The characterised mechanism is metabolic: inhibition of folate-cycle flux, accumulation of AICAR, and consequent AMPK activation. Its nuclear translocation under stress is a separate, intracellular mode of action.
How is it described as an exercise mimetic?
Reynolds et al. (Nature Communications, 2021) showed that MOTS-C rises in muscle and plasma following exercise, and that administering it to aged mice improved measures of running capacity and muscle homeostasis. The term describes an overlap in signalling, not an equivalence to training.
What is the difference between the 10mg and 40mg vials?
Peptide mass only; the material is from the same synthesis and assay standard. The 40mg vial is intended for extended experimental series and gives a higher concentration for a given diluent volume.
How is purity verified?
Every batch is assayed by Bioindustrial Services in Boksburg, an independent biotechnology laboratory, using HPLC. We do not self-certify. The signed certificate of analysis for each batch — lab number, method and assayed result — is published on our quality standards page.
How long does delivery take?
Orders are dispatched from within South Africa with tracking. Timelines by region and courier are set out on our delivery process page.
What is the returns policy?
Unopened vials in original condition may be returned within the stated window; full terms are in our refund policy.
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