MOTS-c is a 16-amino-acid peptide with an unusual origin: it is encoded within mitochondrial DNA, in a short open reading frame inside the 12S rRNA gene, rather than in the nuclear genome like almost every other peptide in this catalogue.
Why the origin matters
Mitochondria were once free-living bacteria and retain their own small genome. For decades that genome was assumed to encode only components of the respiratory chain. The discovery of mitochondrial-derived peptides — of which MOTS-c is the best studied — showed the mitochondrion also issues signalling molecules that act on the rest of the cell.
That reframes the organelle from a passive power plant into something that reports its own state outward.
Mechanism
MOTS-c activates AMP-activated protein kinase (AMPK), the cell’s principal energy sensor. AMPK activation shifts metabolism toward catabolic, ATP-generating pathways and away from anabolic consumption. MOTS-c has also been described translocating to the nucleus under metabolic stress, where it influences transcription of adaptive genes.
Research context
Work has centred on metabolic regulation, insulin sensitivity and exercise physiology in preclinical models. Human data is limited, and observational work associating circulating MOTS-c levels with metabolic status should not be read as demonstrating that supplementing it produces those states.
Supplied lyophilised. See our reconstitution protocol for handling technique and diluent selection.
Every batch ships with a third-party certificate of analysis. View MOTS-c and its current COA.
At a glance
| Property | Detail |
|---|---|
| Full name | Mitochondrial open reading frame of the 12S rRNA, type c |
| Length | 16 amino acids |
| Sequence | MRWQEMGYIFYPRKLR |
| Molecular weight | About 2,175 Da |
| Encoded by | Mitochondrial DNA (12S rRNA region) |
| First described | 2015, in Cell Metabolism |
| Primary pathway studied | AMPK activation via the folate cycle and AICAR |
How MOTS-c reaches AMPK
The route to AMPK is indirect. In the original cell studies, MOTS-c inhibited the folate cycle and the linked de novo purine synthesis pathway. That caused the purine intermediate AICAR to build up, and AICAR is a well-known AMPK activator. This is why MOTS-c is often described as acting on metabolism through a metabolite rather than through a classic cell-surface receptor.
Moving into the nucleus under stress
Later work reported that under metabolic stress, such as glucose restriction or oxidative stress, MOTS-c moves from the cytoplasm into the nucleus. There it was associated with changes in the expression of nuclear genes, including antioxidant-response genes regulated through NRF2. This made MOTS-c one of the first examples of a mitochondrial-encoded peptide that appears to influence the nuclear genome directly.
Exercise and ageing research
Several preclinical studies have linked MOTS-c to physical activity. In mouse models, MOTS-c expression rose in skeletal muscle after exercise, and studies in older animals examined its relationship to physical capacity and muscle metabolism. Circulating levels have also been reported to differ with age in some cohorts. These findings come from laboratory and animal models; the material described here has not been evaluated for any clinical use.
The mitochondrial-derived peptide family
MOTS-c belongs to a small group of signalling peptides encoded in mitochondrial DNA. The other well-studied members are:
- Humanin, a 24-amino-acid peptide from the 16S rRNA region, studied mainly in models of cell survival and stress resistance.
- SHLP1 to SHLP6 (small humanin-like peptides), also encoded in the 16S rRNA region, with varied effects reported in cell models.
MOTS-c is the only member of this group encoded in the 12S rRNA region, and the one most studied for metabolic signalling.
Common questions
Is MOTS-c a hormone?
It is sometimes called a mitochondrial hormone, or mitokine, because it has been detected in circulation and acts on cells beyond the mitochondrion that produced it. That description is still a research framing rather than an established classification.
How is MOTS-c research material verified?
Each batch is checked by HPLC for purity and by mass spectrometry for identity. The expected mass is about 2,175 Da. See our guide to HPLC vs mass spectrometry for what each test shows.
Research use only
Isla Longevity supplies this compound for laboratory research use only. It is not approved by the FDA for human or veterinary use and is not for human consumption. This article summarises published research and is not medical guidance.
