Molecular data
| Molecular formula | C101H152N28O25S2 |
|---|---|
| Molecular weight | 2174.64 Da |
| Sequence | MRWQEMGYIFYPRKLR |
| Sequence length | 16 residues |
| Physical form | Lyophilized Powder |
| Available sizes | 10mg |
How it works
AMP-Activated Protein Kinase Signaling
MOTS-c activates AMP-activated protein kinase (AMPK) in skeletal muscle, adipose tissue, and liver. AMPK is a master metabolic sensor that responds to cellular energy status. MOTS-c–induced AMPK activation in preclinical models was associated with increased glucose uptake, fatty acid oxidation, and mitochondrial biogenesis signaling.
- Direct AMPK phosphorylation (Thr172) in skeletal muscle
- Downstream activation of PGC-1α and mitochondrial biogenesis
- GLUT4 translocation and glucose uptake measured
Mitochondria-to-Nucleus Retrograde Signaling
MOTS-c is encoded within the 12S rRNA gene of the mitochondrial genome — a discovery that established mitochondria as an endocrine organ capable of producing bioactive peptides. Under metabolic stress, MOTS-c translocates from mitochondria to the nucleus where it acts as a transcriptional regulator, modulating antioxidant response element (ARE) gene expression.
- Encoded in mitochondrial DNA (12S rRNA gene region)
- Nuclear translocation under metabolic stress conditions
- Modulates ARE-driven antioxidant gene expression
Metabolic Homeostasis & Exercise Signaling
MOTS-c levels rise in response to exercise, and in mouse models several exercise-associated metabolic measures were recorded following exogenous MOTS-c — insulin sensitivity, adiposity and endurance — including in sedentary animals. It also acts on the folate cycle and purine synthesis under stress, redirecting metabolic flux.
- Endogenous levels increase with aerobic exercise
- Insulin sensitivity studied in rodent metabolic models
- Inhibits AICAR-independent AMPK activation via folate cycle
What the research shows
Insulin Sensitivity Models
In high-fat diet mouse models, insulin sensitivity, fat accumulation and glucose tolerance were measured following MOTS-c administration, with skeletal muscle AMPK activation as the proposed mediator.
Age-Related Metabolic Decline
Circulating MOTS-c levels decline with age in both humans and rodents. In aged mouse models, physical performance and metabolic flexibility measures were recorded following exogenous MOTS-c, and are studied in the context of mitochondrial-nuclear communication.
Exercise Mimicry
Circulating MOTS-c rises with aerobic exercise in humans. In sedentary mouse models, energy metabolism, mitochondrial biogenesis markers and endurance measures were recorded following exogenous MOTS-c.
mtDNA Variation & Ageing Cohorts
Population studies identified MOTS-c variants (particularly R150Q) enriched in elderly Japanese cohorts. Sequence variation correlates with metabolic markers, which is why mitochondrial peptide biology is studied in ageing research.
Specification
| Full Name | Mitochondrial Open Reading Frame of the 12S rRNA-c |
|---|---|
| Sequence | MRWQEMGYIFYPRKLR |
| Amino Acids | 16 residues |
| Molecular Weight | 2174.6 Da |
| Gene Origin | Mitochondrial 12S rRNA (mt-RNR1) |
| Primary Target | AMPK activation; folate cycle; nuclear ARE pathways |
| Form | Lyophilized powder (5mg) |
| Purity | ≥99% (HPLC verified) |
| Testing | Third-party HPLC, Mass Spec, Endotoxin |
| Storage | -20°C for long-term stability |
| Solubility | Bacteriostatic water or sterile saline |
| COA | Included with every order |
Frequently asked questions
What is MOTS-c and where does it come from?
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome — specifically in the 12S ribosomal RNA gene. Discovered in 2015 by researchers at USC led by Dr. Changhan David Lee, it was one of the first identified mitochondrial-derived peptides (MDPs). Unlike most mitochondrial proteins, MOTS-c is translated from a small open reading frame within non-coding RNA, establishing a new category of regulatory peptides originating from the organelle long considered only a metabolic powerhouse.
How does MOTS-c act as an exercise mimetic?
Circulating MOTS-c levels in humans and rodents rise in response to aerobic exercise. MOTS-c activates AMPK — the same energy sensor activated by exercise — in skeletal muscle and other metabolic tissues. In preclinical studies, sedentary mice given exogenous MOTS-c showed metabolic changes overlapping those of exercise training: insulin sensitivity, fatty acid oxidation, mitochondrial biogenesis markers and endurance were all measured. This overlap is why MOTS-c is studied in metabolic biology.
What is the relationship between MOTS-c and aging?
MOTS-c levels decline with age in both humans and rodents, inversely correlating with age-related metabolic markers. Population genetic studies identified a MOTS-c variant (R150Q, also called K14Q in some notation systems) enriched in elderly Japanese men. In aged mouse models, physical performance and metabolic flexibility measures were recorded following exogenous MOTS-c, which is why it is studied in ageing biology.
How does MOTS-c activate AMPK without exercise?
MOTS-c activates AMPK through an indirect mechanism involving the folate cycle. Under metabolic stress, MOTS-c inhibits the enzyme MTHFR (methylenetetrahydrofolate reductase) in the folate-methionine cycle. This disrupts purine nucleotide biosynthesis, causing accumulation of ZMP (5-aminoimidazole-4-carboxamide ribonucleoside monophosphate) — a known AMPK activator. This AICAR-independent pathway for AMPK activation is one of the key mechanistic findings distinguishing MOTS-c from other metabolic peptides.
Are there human studies on MOTS-c?
Human research on MOTS-c primarily consists of observational and correlational studies measuring circulating MOTS-c levels in various populations. These have shown associations between MOTS-c levels and: exercise status, aging, insulin resistance, and cardiovascular disease. Human genetic studies have identified longevity-associated MOTS-c variants. However, no randomized controlled trials of exogenous MOTS-c administration in humans have been completed or published as of 2024.
How should MOTS-c be stored and handled for research?
Store lyophilized MOTS-c at -20°C, protected from light and humidity, and minimize freeze-thaw cycles. MOTS-c is water-soluble, making it suitable for aqueous research systems. For cell culture experiments, filter-sterilize laboratory solutions before use. Always consult published protocols for concentration-specific guidance.
For laboratory research use only. Not a drug, supplement, or medical product; not for human or animal use. All findings referenced are from published preclinical/laboratory research.