On this pageMOTS-c Key Facts
Short answer: MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome. It was described in 2015 by researchers at the University of Southern California and belongs to the family of mitochondrial-derived peptides, alongside humanin.
This page is a laboratory reference: identity data, how MOTS-c is encoded, the signaling pathways it is used to study, common in vitro methods, and what its Certificate of Analysis should show. NuRev supplies MOTS-c in 10 mg and 40 mg vials for laboratory research use only.
MOTS-c Key Facts
| Name | MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) |
|---|---|
| Sequence | MRWQEMGYIFYPRKLR (16 residues) |
| CAS number | 1627580-64-6 |
| Molecular formula | C101H152N28O22S2 |
| Molecular weight | 2174.62 g/mol |
| Encoded by | A short open reading frame in the mitochondrial 12S rRNA gene (MT-RNR1) |
| Class | Mitochondrial-derived peptide |
| Research format | Lyophilized peptide in a sealed vial |
Reference values identify the free peptide. Salt forms such as the acetate have a different formula and molecular weight, so confirm identity and purity against the batch Certificate of Analysis.
What Is MOTS-c?
Most proteins in a cell are encoded by nuclear DNA. Mitochondria keep a small genome of their own, and short open reading frames inside it can produce small peptides. MOTS-c was identified by searching the mitochondrial 12S rRNA gene for such reading frames; one of them encodes the 16-residue peptide now called MOTS-c.
Because it originates in the mitochondrion but has been detected in the cytoplasm, the nucleus and the circulation in preclinical models, MOTS-c is studied as a possible signal between mitochondria and the rest of the cell, sometimes described as a mitochondrial "retrograde" signal.
MOTS-c and Other Mitochondrial-Derived Peptides
MOTS-c is one of several mitochondrial-derived peptides (MDPs) described since the early 2000s:
| Peptide | Encoded in | Length |
|---|---|---|
| Humanin | 16S rRNA (MT-RNR2) | 21–24 residues |
| SHLP1–6 (small humanin-like peptides) | 16S rRNA (MT-RNR2) | 20–38 residues |
| MOTS-c | 12S rRNA (MT-RNR1) | 16 residues |
MDP research asks how these peptides are translated (MOTS-c is thought to be translated in the cytoplasm using the standard genetic code), how they leave the mitochondrion, and which cellular pathways they act on.
MOTS-c Signaling: Folate Metabolism, AICAR and AMPK
The pathway most often studied with MOTS-c runs through one-carbon metabolism:
- MOTS-c has been reported to inhibit the folate–methionine pathway and the de novo purine synthesis pathway that depends on it.
- This leads to accumulation of the purine intermediate AICAR (5-aminoimidazole-4-carboxamide ribonucleotide).
- AICAR is a known activator of AMP-activated protein kinase (AMPK), a central sensor of the cell’s AMP/ATP ratio.
A second line of work reports that, under metabolic stress in cell models, MOTS-c moves into the nucleus and influences the expression of nuclear genes, including antioxidant-response genes. How these two observations fit together, and which steps are direct binding events, are open questions in the field.
How MOTS-c Is Studied in the Laboratory
Common in vitro and preclinical approaches include:
- Cell-based signaling assays: western blot for phosphorylated AMPK and its substrate ACC after MOTS-c exposure, with AMPK inhibitors or knockdown as controls.
- Metabolite analysis: LC-MS measurement of folate-pathway and purine intermediates, including AICAR.
- Localization studies: immunofluorescence or cell fractionation to track MOTS-c between cytoplasm and nucleus.
- Gene-expression analysis: qPCR or RNA-seq of nuclear target genes under stress conditions.
- Mitochondrial readouts: oxygen consumption rate on extracellular flux analyzers.
Scrambled-sequence peptides of the same composition are a useful negative control for sequence-specific effects.
Characterization and Quality Documentation for MOTS-c
NuRev lots are tested by independent third-party laboratories. A useful Certificate of Analysis for a research peptide shows:
- Identity by mass spectrometry, matched to the expected molecular weight
- Purity by HPLC, with the chromatogram
- A lot number identical to the vial label, the test date and the laboratory
Posted lots are in the COA library; others are available on request. See also HPLC testing and how to read a peptide COA.
For MOTS-c, the expected average mass is about 2174.6 Da; electrospray MS typically shows multiply charged ions, so compare the deconvoluted mass with the reference value.
Storage and Handling of Lyophilized MOTS-c
MOTS-c contains two methionine residues, which can oxidize. General practice for lyophilized peptides applies:
- Store the sealed vial at −20 °C, protected from light and moisture. Short-term storage at 2–8 °C is acceptable.
- Let the vial reach room temperature before opening to limit condensation.
- Dissolve in a solvent suited to the assay, mix gently rather than vortexing hard, and divide solutions into single-use aliquots.
- Avoid repeated freezing and thawing, and record the lot number for every experiment so results trace to the Certificate of Analysis.
More detail is in peptide storage best practices and reconstitution guidance.
NuRev supplies this material for laboratory research use only. It is not for human or veterinary use.
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.