Maple MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino acid mitochondrial-derived peptide first identified by Lee et al. in 2015. Unlike most bioactive peptides that are encoded by nuclear DNA, MOTS-c is encoded within the mitochondrial genome, specifically within the 12S rRNA gene. This origin makes MOTS-c part of a small but growing class of mitochondrial-derived peptides (MDPs) that function as retrograde signaling molecules, communicating mitochondrial status to nuclear gene expression and systemic metabolism.
Maple Research Labs supplies research-grade MOTS-c to Canadian laboratories, universities, and documented research buyers. Every batch ships with an independent third-party Certificate of Analysis confirming identity and purity.
For research purposes only. Not for human consumption. Not for diagnostic or therapeutic use.
Molecular Profile
| Parameter | Value |
|---|---|
| Sequence | MRWQEMGYIFYPRKLR |
| CAS Number | 1627580-64-6 |
| Molecular Formula | C101H152N26O22S2 |
| Molecular Weight | 2174.6 Da |
| Origin | Mitochondrial genome (12S rRNA gene) |
| Purity | ≥99% (HPLC) |
| Storage | -20°C, lyophilized, desiccated, protected from light |
Primary Research Mechanisms
AMPK Pathway Activation
The central mechanism documented for MOTS-c involves activation of AMP-activated protein kinase (AMPK), the master cellular energy sensor. In the original characterization by Lee et al. (2015), MOTS-c treatment activated AMPK signaling in skeletal muscle cells, increasing glucose uptake and fatty acid oxidation. The proposed pathway involves MOTS-c inhibition of the folate cycle and de novo purine biosynthesis, leading to accumulation of the intermediate AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), an endogenous AMPK activator. This positions MOTS-c as a metabolic regulator that links mitochondrial genome-encoded signaling to cellular energy homeostasis.
Nuclear Translocation and Gene Regulation
Research has demonstrated that MOTS-c translocates to the nucleus under conditions of metabolic stress. Kim et al. (2018) showed that upon glucose restriction or oxidative stress, MOTS-c accumulates in the nucleus where it interacts with antioxidant response element (ARE) motifs and modulates the expression of genes involved in cellular stress adaptation. This nuclear translocation represents a direct retrograde signaling mechanism from the mitochondria to nuclear gene regulation, a pathway that was poorly understood before the discovery of MDPs.
Insulin Sensitivity and Glucose Metabolism
In preclinical models, MOTS-c administration improved glucose tolerance and insulin sensitivity. Lee et al. demonstrated that MOTS-c treatment prevented age-dependent and high-fat diet-induced insulin resistance in mouse models. The mechanism appears to involve both direct AMPK-mediated glucose uptake enhancement and indirect effects through improved mitochondrial function and reduced inflammatory signaling in metabolically active tissues.
Exercise Mimetic Properties
MOTS-c has been characterized as an exercise-responsive mitochondrial signal. Reynolds et al. (2021) demonstrated that circulating MOTS-c levels increase during exercise in humans, and that MOTS-c treatment in sedentary aged mice improved physical capacity. The peptide’s ability to activate AMPK, enhance glucose uptake, and improve mitochondrial function in skeletal muscle mirrors several molecular responses typically induced by physical exercise, leading to its classification as a potential exercise mimetic in research contexts.
Mitochondrial-Derived Peptides: Research Context
MOTS-c belongs to the mitochondrial-derived peptide (MDP) family alongside humanin and SHLPs (small humanin-like peptides). While humanin (encoded within the 16S rRNA gene) was the first MDP identified, MOTS-c is the first MDP shown to regulate nuclear gene expression through direct nuclear translocation. This family of peptides has reshaped understanding of mitochondrial function, demonstrating that mitochondria are not merely energy-producing organelles but active participants in intercellular and intracellular signaling through peptide-mediated communication.
Product Specifications
| Specification | Detail |
|---|---|
| Peptide | MOTS-c |
| CAS Number | 1627580-64-6 |
| Purity | ≥99% (HPLC verified) |
| Form | Lyophilized powder |
| Available Sizes | 10mg |
| COA | Third-party Certificate of Analysis included with every order |
| Storage | -20°C, desiccated, protected from light |
| Shipping | Same-day processing from Canada |
| Use | For research purposes only |
View MOTS-c product page and COA | How to read a Certificate of Analysis
Frequently Asked Questions
What is MOTS-c and why is it significant in peptide research?
MOTS-c is a 16-amino acid peptide encoded within the mitochondrial genome, making it one of the first identified mitochondrial-derived peptides (MDPs). Its significance lies in demonstrating that the mitochondrial genome directly encodes bioactive signaling molecules that regulate nuclear gene expression, cellular metabolism, and systemic energy homeostasis through AMPK pathway activation.
How does MOTS-c differ from other metabolic research peptides?
Unlike GLP-1 receptor agonists (semaglutide, tirzepatide) that work through cell-surface receptor binding, MOTS-c operates through intracellular AMPK activation and direct nuclear translocation. It is also unique in being mitochondrially encoded rather than nuclear-encoded, representing an entirely different class of metabolic signaling molecule.
Can I buy MOTS-c peptide in Canada?
Yes. Maple Research Labs is a Canadian supplier of research-grade MOTS-c verified at 99%+ purity via independent HPLC analysis. Orders ship from within Canada with same-day processing and include a batch-specific Certificate of Analysis. MOTS-c is sold exclusively for in-vitro and preclinical research use.
What is the relationship between MOTS-c and exercise research?
Research has shown that circulating MOTS-c levels increase during exercise in humans. In preclinical models, MOTS-c treatment activates AMPK, enhances glucose uptake, and improves mitochondrial function in skeletal muscle, mirroring molecular responses typically associated with physical exercise. This has led to its classification as a potential exercise mimetic in research settings.
Related Research Resources
- GLP-1 & Incretin Pathway Research — Metabolic receptor agonist peptides
- BPC-157 Research Overview — Cytoprotection and tissue repair
- Understanding Certificates of Analysis — COA interpretation guide
- All Research Peptides — Complete compound catalog
For research purposes only. Not for human consumption. Not for diagnostic or therapeutic use.