What Is MOTS-c? The Mitochondrial-Derived Peptide: Sequence, CAS Number and Research Literature

By the Zen Well Labs Research Team · Last reviewed September 2026 · For laboratory research reference only

Short answer: MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide with the sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR), a molecular weight of about 2174.6 Da and CAS number 1627580-64-6. It is encoded by a short open reading frame inside the mitochondrial 12S rRNA gene and was first described by Lee and colleagues in Cell Metabolism in 2015. It is studied as a regulator of cellular metabolism, chiefly through AMPK signalling. It is not FDA-approved; Zen Well Labs sells it for in-vitro laboratory research only.

MOTS-c at a glance

Full name	Mitochondrial open reading frame of the 12S rRNA type-c
Class	Mitochondrial-derived peptide (MDP)
Length	16 amino acids
Sequence (one-letter)	MRWQEMGYIFYPRKLR
Molecular formula	C₁₀₁H₁₅₂N₂₈O₂₂S₂
Molecular weight	≈2174.6 Da
CAS number	1627580-64-6
Encoded by	A short ORF within the mitochondrial MT-RNR1 (12S rRNA) gene
Typical supplied form	Lyophilized powder

Why MOTS-c is scientifically interesting

The human mitochondrial genome was long thought to encode just 13 proteins. MOTS-c belongs to a small group of mitochondrial-derived peptides — alongside humanin and the SHLPs — that are encoded by short open reading frames hidden inside mitochondrial rRNA genes. Their discovery suggested that mitochondria send peptide signals to the rest of the cell, and possibly to other tissues.

What has the published research looked at?

AMPK activation via the folate cycle. In the original 2015 paper, Lee et al. reported that MOTS-c inhibits the folate–methionine cycle in cultured cells, leading to accumulation of the endogenous AMPK activator AICAR and activation of AMPK, with downstream effects on glucose utilisation.
Diet-induced metabolic models. The same paper reported effects on insulin sensitivity and weight gain in mice fed a high-fat diet.
Nuclear translocation under stress. Kim and colleagues (Cell Metabolism, 2018) showed that MOTS-c moves to the nucleus in response to metabolic stress and influences nuclear gene expression — an example of mitochondria-to-nucleus (retrograde) signalling by a mitochondrial-encoded factor.
Exercise and ageing. Reynolds et al. (Nature Communications, 2021) reported that endogenous MOTS-c levels rise with exercise in humans and examined physical performance in aged mice.

These are mechanistic and preclinical findings. MOTS-c has not been approved by the FDA for any use.

Handling notes specific to MOTS-c

Oxidation-sensitive residues. The sequence contains two methionines and a tryptophan, all prone to oxidation. Limit air and light exposure and avoid repeated freeze–thaw of solutions.
Basic, positively charged peptide. With three arginines and a lysine, MOTS-c is strongly basic and generally dissolves readily in aqueous media; like other cationic peptides it can adsorb to glass and some plastics at low concentrations, so low-bind tubes are a sensible precaution.
Store lyophilized powder sealed, dry and dark at −20 °C. See the storage and stability guide.

Frequently asked questions

What does MOTS-c stand for?

Mitochondrial open reading frame of the 12S rRNA type-c. The name describes where the peptide is encoded in the mitochondrial genome.

What is the amino acid sequence of MOTS-c?

Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg, or MRWQEMGYIFYPRKLR in one-letter code. It is 16 residues long.

What is the molecular weight and CAS number of MOTS-c?

Approximately 2174.6 Da, CAS 1627580-64-6.

How does MOTS-c activate AMPK?

According to the original 2015 report, MOTS-c inhibits the folate–methionine cycle, which raises intracellular AICAR, an endogenous activator of AMPK.

Is MOTS-c FDA-approved?

No. MOTS-c is not approved by the FDA for any use. Zen Well Labs sells it for in-vitro laboratory research only.

References

Lee C, Zeng J, Drew BG, 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, Son JM, Benayoun BA, Lee C. 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, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications. 2021;12:470.

Research use only. All products sold by Zen Well Labs are intended strictly for in-vitro laboratory research. They are not drugs, foods, cosmetics or dietary supplements, are not approved by the FDA for any use, and are not for human or veterinary use. Nothing on this page is medical advice, and nothing here describes or recommends administration to humans or animals.