MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome — the first mitochondria-derived peptide shown to have systemic hormonal activity. It translocates to the nucleus under metabolic stress, activates AMPK, and regulates folate-methionine metabolism. Research focuses on insulin sensitization, exercise mimicry, anti-aging, and metabolic health.
CAS 1627580-64-6 | MW 2174.5 Da | Sequence: MRWQEMGYIFYPRKLRMOTS-c activates AMPK in skeletal muscle and fat, mimicking exercise-induced metabolic signalling without physical activity.
Under metabolic stress, MOTS-c regulates the folate cycle by inhibiting the de novo purine synthesis, redirecting carbon flux to methylation.
On heat or oxidative stress, MOTS-c translocates to the nucleus and regulates nuclear gene expression — a unique mitochondrial-nuclear crosstalk.
SC administration in aged mice improved exercise capacity, muscle function, and metabolic parameters comparable to physical training.
Lee et al. (2015) identified MOTS-c as a mitochondria-encoded peptide that regulates insulin sensitivity and metabolic homeostasis, establishing it as a new class of bioactive peptide.
Cell Metab. 2015;21(3):443–454Lee et al. (2019) demonstrated that MOTS-c administration to aged mice restored muscle function and exercise capacity, proposing mitochondrial peptides as potential exercise mimetics for sarcopenia research.
Nat Commun. 2019;10(1):4148MOTS-c levels are elevated during metabolic stress and exercise in humans, correlating with metabolic health markers and suggesting a hormonal signalling role for mitochondrial peptides.
Nat Commun. 2019;10(1):4148Published murine studies use 5 mg/kg SC or IP 3x/week. In vitro metabolic studies use 1–10 µM in cell culture. Endpoints: AMPK phosphorylation, glucose uptake (2-NBDG), oxygen consumption rate (Seahorse), and grip strength/treadmill performance. Compare metabolic outcomes to exercise-trained vs sedentary controls.
| Full Name | MOTS-c (Mitochondrial ORF of 12S rRNA-c) |
| CAS Number | 1627580-64-6 |
| Molecular Formula | C₁₀₀H₁₈₂N₃₄O₂₅S |
| Molecular Weight | 2174.5 Da |
| Sequence | MRWQEMGYIFYPRKLR |
| Purity | ≥99% by HPLC |
| Storage | −20°C, desiccated |
