MOTS-C

What is MOTS-C?

MOTS-C is a 16 amino acid mitochondrial derived peptide encoded by a short open reading frame within the 12S rRNA (MT-RNR1) region of mitochondrial DNA, sequence MRWQEMGYIFYPRKLR. The name abbreviates mitochondrial open reading frame of the twelve S rRNA type-c, and the literature generally writes it MOTS-c. Characterised by Lee and colleagues in Cell Metabolism in 2015, it was the second peptide whose short open reading frame was mapped to the mitochondrial genome after humanin, and the first assigned a defined metabolic mechanism. Supplied as lyophilised powder for in-vitro research use only.

MOTS-C vs Humanin and the Mitochondrial Derived Peptide Family

Mitochondrial derived peptides (MDPs) are encoded inside mitochondrial DNA rather than the nuclear genome, and are studied as retrograde signals carrying information outward from the mitochondrion. Humanin came first, a 24 residue peptide from the 16S rRNA region investigated mainly for cytoprotective and anti-apoptotic signalling. MOTS-C came second, from the 12S rRNA region, and is mechanistically distinct: it acts on the folate-methionine cycle and de novo purine biosynthesis, raising endogenous AICAR and thereby activating AMPK, and under metabolic stress it translocates into the nucleus and binds antioxidant response element sequences. The SHLP series (SHLP1 to SHLP6) followed from the 16S region. Researchers select MOTS-C when the endpoint is metabolic regulation, AMPK activation driven from upstream nucleotide metabolism, or mitochondrial-nuclear crosstalk; humanin when the endpoint is cytoprotection or apoptosis.

MOTS-C Research Applications

MOTS-C is studied in metabolic and mitochondrial research models covering AMPK signalling, folate-methionine cycle flux, de novo purine biosynthesis and AICAR accumulation, glucose and fatty acid metabolism, skeletal muscle bioenergetics, PGC-1α expression, and mitochondrial-to-nuclear retrograde signalling including NRF2 association and antioxidant response element binding. It also serves as the reference compound in the wider mitokine and mitochondrial derived peptide literature, and in analytical method development where a low molecular weight mtDNA-encoded peptide is needed as a standard.

Reconstitution Guide

Allow vials to reach room temperature, then sterilise the rubber stopper of both the peptide vial and the bacteriostatic water vial with an alcohol swab. Slowly draw your bacteriostatic water into a sterile insulin syringe, then inject it gently down the inner glass wall of the peptide vial, never directly onto the lyophilised powder. Once added, gently swirl the vial in a slow circular motion until fully dissolved. Never shake or vortex. The solution should be clear and colourless. Label the vial with the reconstitution date and store immediately.

See our full peptide reconstitution guide and reconstitution calculator for step-by-step protocol.

Storage Instructions

Lyophilised vials should be stored at -20°C, protected from light and moisture, and remain stable for up to 24 months. Once reconstituted with bacteriostatic water, store the solution at 2-8°C (standard refrigerator) and use within approximately 3 months. For storage beyond that, prepare single-use aliquots at -20°C, where reconstituted peptide remains stable for up to 6 months. Avoid repeated freeze-thaw cycles and always handle under sterile laboratory conditions.

Frequently Asked Questions

Research References

• The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (Cell Metab, 2015)
• The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress (Cell Metab, 2018)
• MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis (Nat Commun, 2021)

Related Research Compounds

• → NAD+ 500mg
• → 5-Amino-1MQ 50mg
• → L-Carnitine 500mg
• → Mitochondrial Stack
• → Bacteriostatic Water 10ml