MOTS-C

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a mitochondrial-derived peptide (MDP) discovered by Changhan Lee and Pinchas Cohen at the USC Leonard Davis School of Gerontology in 2015. It is encoded within the mitochondrial 12S rRNA gene and has been studied for its role in metabolic regulation and AMPK pathway activation.

MOTS-c is a 16-amino acid peptide with molecular weight 2174.64 g/mol, encoded by the mitochondrial genome. It is unique among bioactive peptides in that it originates from mitochondrial DNA rather than nuclear DNA, representing an emerging class of mitochondrial-derived peptides (MDPs).

The peptide contains two methionine residues that can undergo oxidation, requiring careful handling and storage to maintain biological activity in research settings.

• Metabolic biology: MOTS-c has been studied for its effects on glucose metabolism and insulin sensitivity in murine models of diet-induced obesity (Lee et al., 2015).
• AMPK pathway: Research has examined MOTS-c's interaction with AMP-activated protein kinase signaling in metabolic regulation.
• Exercise biology: Studies have investigated MOTS-c as an exercise-mimetic peptide, examining skeletal muscle metabolism effects.
• Aging research: Investigations into MOTS-c levels across age groups and its potential role in age-related metabolic changes.

• AMPK pathway activation and downstream metabolic regulation
• Folate-methionine cycle interaction affecting cellular metabolism
• AICAR accumulation and de novo purine biosynthesis pathway
• Nuclear translocation and stress-responsive gene regulation

Key preclinical findings:

Lee et al. (2015, Cell Metabolism): MOTS-c at 5 mg/kg/day (IP) prevented diet-induced obesity and insulin resistance in C57BL/6 mice on high-fat diet. Activated AMPK in skeletal muscle and improved glucose tolerance by 30%.

Reynolds et al. (2021, Nature Communications): MOTS-c translocated to the nucleus under metabolic stress (glucose restriction, exercise). In skeletal muscle, MOTS-c regulated adaptive gene expression through ARE/ETS motifs. Exercise increased endogenous MOTS-c levels 2-fold in exercise-physiology research.

Kim et al. (2018): MOTS-c improved insulin sensitivity in mouse models of age-related metabolic decline. Circulating MOTS-c levels declined 50% with aging (3 vs 18 months).

Typical in vitro concentrations: 0.1-10 µM. In vivo: 5-15 mg/kg/day (rodent studies).

MOTS-c is one of the first mitochondrial-derived peptides (MDPs) to be characterized as an endocrine signal from the mitochondrial genome.

Form: Lyophilized powder, 5mg per vial
Appearance: White powder
Molecular Weight: 2174.64 g/mol
For In Vitro Research Use Only

Laboratory Preparation:
Add sterile diluent to vial. Gently swirl until dissolved. Contains methionine residues susceptible to oxidation.

Solubility Profile: Soluble in water (~5 mg/mL), PBS.

Stability: Lyophilized stable 24 months at -20°C. Solution: 14-30 days at 2-8°C. Protect from oxidants and UV.

Analytical Testing: HPLC, ESI-MS, LAL endotoxin, USP sterility.

This product is for laboratory and in vitro research only. Not for human or animal use.

This content was prepared for informational purposes based on published preclinical research. It does not constitute medical advice or product efficacy claims.

1. 1
   Lee C, et al. "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance." Cell Metab. 2015;21(3):443-54. PubMed: 25738459 PubMed
2. 2
   Reynolds JC, et al. "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis." Nat Commun. 2021;12(1):470. PubMed: 33473109 PubMed
3. 3
   Kim SJ, et al. "Mitochondrial peptides modulate mitochondrial function during cellular senescence." Aging. 2018;10(6):1239-56. PubMed: 29885261 PubMed