What is MOTS-C?

MOTS-C (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino acid peptide encoded by a short open reading frame inside mitochondrial DNA, not the nuclear genome. Its sequence is MRWQEMGYIFYPRKLR. In published laboratory work it is used to study mitochondrial–nuclear signalling, AMPK-related energy sensing, and metabolic pathway biochemistry.

The peptide was first described in 2015 by Lee, Cohen and colleagues in Cell Metabolism:
The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance.

Property	Value
Full name	Mitochondrial open reading frame of the 12S rRNA type-c
Class	Mitochondrial-derived peptide (MDP)
Sequence	MRWQEMGYIFYPRKLR
Length	16 amino acids
CAS	1627580-64-6
Formula	C₁₀₁H₁₅₂N₂₈O₂₂S₂
Molecular weight	2174.6 g/mol (free peptide)
Encoded by	MT-RNR1 (mitochondrial 12S rRNA)
Typical lab form	Lyophilised powder

Chemical registry details are also listed on PubChem (MOTS-c, CID 146675088).

What MOTS-C actually is

Most peptides used in a lab are encoded by nuclear genes and made on cytosolic ribosomes. MOTS-C is different. It belongs to a small family of mitochondrial-derived peptides (MDPs). The sequence sits in a 51-base-pair short open reading frame (sORF) within the mitochondrial 12S rRNA gene (MT-RNR1).

Translation is not done with the mitochondrial genetic code. Using that code, the same DNA stretch would produce tandem start and stop signals. The peptide is translated in the cytoplasm with the standard genetic code after the transcript leaves the mitochondrion. That is why a synthetic laboratory reagent can be made as a linear 16-mer matching the human sequence:

Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
H-MRWQEMGYIFYPRKLR-OH

The chain is short, basic (several Arg/Lys residues), and chemically sensitive. Positions 1 and 6 are methionine and position 3 is tryptophan. Those residues oxidise more easily than the rest of the sequence, which matters for storage and handling.

It is not the same molecule as humanin. Humanin is a different mitochondrial-derived peptide. MOTS-C is also not a GLP-1, GIP, or growth-hormone analogue.

Discovery and published research context

MOTS-C was first characterised in 2015 at the University of Southern California and reported in Cell Metabolism. That paper identified a previously unrecognised sORF in 12S rRNA and described the peptide as a mitochondrial signal that can influence metabolic homeostasis in experimental systems.

Later laboratory work has examined:

AMPK (AMP-activated protein kinase) activation
Folate-cycle / de novo purine biosynthesis and AICAR-related signalling
Glucose handling and insulin-sensitivity assays in cells and animal models
Skeletal-muscle and metabolic-stress models
Observational work on circulating MOTS-C and age
Nuclear translocation and stress-responsive transcription programmes under metabolic stress

This is preclinical and mechanistic literature. MOTS-C is not an approved therapeutic good in Australia. Early clinical work on analogues does not change the status of research-grade MOTS-C as a laboratory reagent.

How researchers think about the mechanism

In published models, MOTS-C is often discussed as a mitohormone — a peptide signal originating from mitochondria that can act on other parts of the cell.

A commonly cited pathway, including in the 2015 discovery paper, is:

Interference with the folate cycle and linked purine synthesis
Accumulation of intermediates such as AICAR
Activation of AMPK, the cell’s energy-status sensor
Downstream changes in glucose uptake and metabolic gene expression in experimental systems

Under metabolic stress, some studies report MOTS-C moving from the cytoplasm into the nucleus and interacting with stress-response transcription programmes. That is why it appears in papers on mitochondrial–nuclear communication, not only on metabolism in the everyday sense.

For a research supplier, the useful point is simple: MOTS-C is a defined 16-mer used to probe those pathways. It is not a finished drug product.

Typical laboratory applications

Research groups use MOTS-C as a reagent in:

Mitochondrial signalling and MDP biology
AMPK phosphorylation and energy-sensing assays
Glucose uptake and insulin-signalling experiments in cultured myotubes, hepatocytes or adipocytes
Diet- and age-related metabolic models in animals (institutional ethics approval required)
Comparative work with other metabolic research peptides, where the question is mechanism, not clinical use

It is supplied as a lyophilised chemical for reconstitution in sterile laboratory solvents or buffers according to the researcher’s protocol.

Chemical and handling notes that matter in the lab

Identity. Confirm the batch against CAS 1627580-64-6, sequence MRWQEMGYIFYPRKLR, and mass near 2174.6 Da (free peptide). Mass spectrometry should match the expected monoisotopic mass. Salt form (acetate or TFA) changes the observed mass; the CoA should state the form.

Purity. Research-grade material is typically specified at ≥98% by HPLC, with many batches ≥99%. HPLC purity is not the same as net peptide content. A vial labelled 20 mg may contain peptide plus counter-ions and residual moisture. Use the CoA for both purity and content if your assay is concentration-critical.

Oxidation. Met and Trp make this sequence more prone to oxidation than a peptide without those residues. Keep lyophilised vials dry, sealed, and protected from light. Limit air exposure after opening.

Storage (powder).

Long term: −20 °C, original sealed vial
Short term: 2–8 °C if the vial stays dry
Avoid repeated warm/cold cycling

After reconstitution. Store solution at 2–8 °C and use promptly. If the protocol needs longer storage, aliquot and freeze; do not freeze–thaw the same aliquot repeatedly.

Shipping. Temperature-sensitive. Cold-pack / insulated packaging is appropriate for Australian domestic transit. Refrigerate or freeze on arrival as specified on the product page.

How MOTS-C compares with other catalogue peptides

This is a classification aid for researchers, not a use guide.

Peptide	Research class	Length	Distinct point
MOTS-C	Mitochondrial-derived peptide	16 aa	Encoded in mtDNA; AMPK / metabolic signalling studies
Semaglutide	GLP-1 receptor agonist analogue	31 aa	Incretin-pathway research
Tirzepatide	Dual GIP / GLP-1 agonist analogue	39 aa	Dual incretin receptor studies
Retatrutide	Triple agonist analogue	39 aa	Multi-receptor metabolic research
BPC-157	Healing / tissue-repair peptide	15 aa	Tissue-repair models
TB-500	Thymosin β4 fragment	fragment / related	Cytoskeletal and repair models
HGH (somatropin)	Growth hormone	191 aa protein	Somatotropic-axis research