MOTS-c: Structure, Research Overview and Specifications
MOTS-c is a 16-amino-acid peptide encoded not in the cell nucleus but in mitochondrial DNA. It belongs to a small family of mitochondrial-derived peptides and is studied for its role in cellular energy metabolism, AMPK signalling and the cell’s response to metabolic stress. This page summarises its chemistry, the published research and the specifications of the material we supply.
For in vitro research use only. Not for human or animal use. Nothing on this page is medical advice.
What is MOTS-c?
MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c. It was first described in 2015 by researchers who found that a short sequence inside the mitochondrial 12S ribosomal RNA gene codes for a small, biologically active peptide.
The discovery was notable because mitochondria were long thought to encode only a handful of proteins for their own machinery. MOTS-c showed that mitochondria can also produce signalling peptides that act elsewhere in the cell, including in the nucleus, which is why it is often described as a “mitochondrial hormone” or mitokine in the research literature.
Chemical data
| Name | MOTS-c |
|---|---|
| Full name | Mitochondrial open reading frame of the 12S rRNA type-c |
| Sequence | Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR) |
| Length | 16 amino acids |
| Molecular formula | C101H152N28O22S2 |
| Molecular weight | ≈ 2174.6 g/mol |
| CAS number | 1627580-64-6 |
| Form supplied | Lyophilised (freeze-dried) powder |
Origin: a peptide from mitochondrial DNA
Most proteins in a cell are encoded by nuclear DNA. Mitochondria carry their own small genome, and within it researchers have identified short open reading frames that produce peptides now grouped as mitochondrial-derived peptides (MDPs). The best known are humanin, the small humanin-like peptides (SHLPs) and MOTS-c.
MOTS-c is found in multiple tissues and in circulation, with skeletal muscle studied as a major target tissue. Research has also reported that circulating levels can vary with age and with physical activity, which has made it a subject of interest in research on metabolism and ageing.
Proposed mechanisms studied
- Folate cycle and AICARIn cell models, MOTS-c was reported to inhibit the folate–methionine cycle, leading to accumulation of the metabolite AICAR.
- AMPK activationAICAR accumulation activates AMP-activated protein kinase (AMPK), a central regulator of cellular energy balance and glucose uptake.
- Nuclear translocationUnder metabolic stress, MOTS-c has been observed to move from the cytoplasm into the nucleus, where it can influence gene expression.
- Stress-response genesIn the nucleus, MOTS-c has been linked to regulation of antioxidant response element (ARE) genes alongside the transcription factor NRF2.
What the published research shows
Metabolic regulation in animal models
The original 2015 study reported that MOTS-c treatment in mice fed a high-fat diet was associated with reduced weight gain and improved insulin sensitivity, with skeletal muscle identified as a primary target. These effects were linked to the AMPK pathway described above.
Nuclear signalling under stress
A 2018 study showed that MOTS-c translocates to the nucleus in response to metabolic stress and helps regulate adaptive gene expression, providing evidence for direct communication between mitochondrial and nuclear genomes.
Exercise and physical capacity
A 2021 study reported that MOTS-c levels in skeletal muscle and circulation increased in response to exercise in humans, and that MOTS-c treatment in mice of different ages was associated with improved physical performance in laboratory tests.
Ageing research
Because MOTS-c levels have been reported to decline with age in some studies, it is being investigated in research on age-related metabolic decline. This work remains at an early, mostly preclinical stage.
Limitations of the evidence
- Most findings come from cell culture and rodent models; results in animals do not necessarily translate to humans.
- Human data is largely observational, measuring natural MOTS-c levels rather than testing the peptide itself.
- The full receptor and transport mechanisms of MOTS-c are not yet fully understood.
- The research field is young, with a relatively small number of independent research groups.
Regulatory status
MOTS-c is not approved as a medicine in the UK, EU or US. It is an investigational research compound. The material we supply is sold strictly for in vitro laboratory research and is not intended for human or animal use.
Storage and handling in the lab
- Store lyophilised powder at −20 °C, protected from light and moisture, for long-term stability.
- Allow the vial to reach room temperature before opening to reduce condensation.
- Once reconstituted for experiments, keep refrigerated (2–8 °C) and avoid repeated freeze–thaw cycles.
- MOTS-c contains two methionine residues, which can be prone to oxidation; minimise air exposure of solutions.
Quality
Every batch of MOTS-c we supply is independently tested for purity by Janoshik using HPLC before it is released for sale. Read more on our Quality & Testing page.
Related research compounds
Frequently asked questions
What does MOTS-c stand for?
MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c. It is a 16-amino-acid peptide encoded in mitochondrial DNA.
How is MOTS-c different from most peptides?
Most peptides are encoded by nuclear DNA. MOTS-c is encoded by the mitochondrial genome, making it one of a small group of mitochondrial-derived peptides alongside humanin.
What pathway is MOTS-c associated with?
Research links MOTS-c to the folate cycle and to activation of AMPK, a key regulator of cellular energy metabolism. Under stress it has also been observed to move into the nucleus and influence gene expression.
Is MOTS-c approved for human use?
No. MOTS-c is an investigational compound and is not approved as a medicine in the UK. Our product is supplied strictly for laboratory research.
How should MOTS-c be stored?
Lyophilised MOTS-c should be stored at −20 °C, protected from light and moisture. Reconstituted solutions should be kept refrigerated and not repeatedly frozen and thawed.
References
- Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism. 2015;21(3):443–454.
- 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 Metabolism. 2018;28(3):516–524.
- Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021;12:470.
- Kim SJ, et al. Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging (Albany NY). 2018;10(6):1239–1256.
This page is for scientific information only. Sterling Research Group Ltd supplies MOTS-c strictly for in vitro laboratory research. Not for human or animal use, and not for diagnostic or therapeutic purposes. Questions: [email protected]