MOTS-C — Research Peptide Overview, Specifications, and Sourcing

At-a-Glance Specifications

CAS Number

1627580-64-6

Molecular Weight

1787.0 g/mol

Molecular Formula

C₈₂H₁₃₀N₂₀O₂₃S₂

Amino Acid Sequence

MRWQEMGYIFYPRKLR (16 amino acids)

Purity

≥99% (HPLC verified)

Physical Form

Lyophilized powder

Storage

-20°C lyophilized; 2-8°C reconstituted

Synonyms

Mitochondrial Open Reading Frame of the 12S rRNA-c, Mitochondrial-derived peptide MOTS-c

What Is MOTS-C?

MOTS-C (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a mitochondrial-derived peptide (MDP) consisting of 16 amino acids encoded within the 12S ribosomal RNA gene of mitochondrial DNA. First discovered and characterized by Changhan Lee and Pinchas Cohen at the University of Southern California in 2015, MOTS-C belongs to an emerging class of bioactive peptides produced from short open reading frames within the mitochondrial genome.

The discovery of MOTS-C challenged the longstanding paradigm that mitochondrial DNA primarily encodes only 13 proteins, 22 tRNAs, and 2 rRNAs. MOTS-C, along with humanin and other mitochondrial-derived peptides, revealed a previously unrecognized layer of mitochondrial signaling that communicates cellular metabolic status to the nucleus and other cellular compartments. This retrograde signaling function has positioned MOTS-C as a key molecule in the emerging field of mitochondrial biology and its intersection with aging, metabolism, and cellular stress response.

MOTS-C has been shown to function as a systemic metabolic regulator, with effects on glucose homeostasis, fatty acid metabolism, and cellular stress resistance. Circulating levels of MOTS-C decline with age in humans, mirroring the age-related decline in mitochondrial function and metabolic capacity. This correlation has generated substantial interest in MOTS-C as a research target for understanding the molecular mechanisms linking mitochondrial function to aging and metabolic disease.

For wholesale research suppliers, MOTS-C represents an emerging high-demand compound driven by the rapidly expanding field of mitochondrial biology and longevity research. Academic research institutions, pharmaceutical companies exploring aging biology, and longevity-focused research programs constitute the primary demand base.

Mechanism of Action

MOTS-C operates through several interconnected mechanisms that converge on metabolic regulation, stress resistance, and cellular homeostasis.

AMPK Pathway Activation

MOTS-C activates AMP-activated protein kinase (AMPK), the master cellular energy sensor, through mechanisms that involve modulation of the folate-methionine cycle. Lee et al. (2015) demonstrated that MOTS-C inhibits the folate cycle at the level of AICAR transformylase, leading to accumulation of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide). This AMPK activation drives downstream effects including enhanced glucose uptake, fatty acid oxidation, and mitochondrial biogenesis (PMID: 25738459).

Nuclear Translocation and Gene Regulation

Under conditions of metabolic stress, MOTS-C translocates from the cytoplasm to the nucleus, where it interacts with chromatin and regulates gene expression. Kim et al. (2018) showed that MOTS-C binds to antioxidant response elements (AREs) in the nuclear genome and promotes the expression of protective genes including those involved in glutathione metabolism and oxidative stress defense. This nuclear function represents a novel mechanism of mito-nuclear communication (PMID: 30197299).

Metabolic Regulation

MOTS-C regulates multiple metabolic pathways including glucose metabolism, fatty acid oxidation, and one-carbon metabolism. Research has demonstrated that MOTS-C enhances insulin sensitivity, promotes glucose uptake in skeletal muscle, and modulates hepatic glucose output. These metabolic effects are mediated in part through AMPK activation and in part through direct transcriptional regulation of metabolic genes.

Cellular Stress Resistance

MOTS-C enhances cellular resistance to various stressors including oxidative stress, metabolic stress, and genotoxic stress. Its nuclear translocation during stress conditions activates a protective transcriptional program that upregulates antioxidant defenses, DNA repair pathways, and proteostasis mechanisms. Reynolds et al. (2021) showed that MOTS-C improved physical performance and stress resistance in aging mice, supporting its role as a systemic resilience factor (PMID: 33308478).

Exercise Mimetic Effects

MOTS-C has been described as an exercise-mimetic peptide, activating many of the same molecular pathways activated by physical exercise. Studies have shown that exercise increases circulating MOTS-C levels in humans, and exogenous MOTS-C administration in sedentary animal models produces metabolic improvements similar to those achieved through exercise training.

Research Applications

Aging and Longevity Research

MOTS-C is a primary research tool in the longevity field, with studies examining its effects on lifespan, healthspan, age-related metabolic decline, and cellular senescence. The age-related decline in circulating MOTS-C levels has made it a candidate biomarker and potential intervention target in aging research.

Metabolic Research

MOTS-C is investigated in models of insulin resistance, type 2 diabetes, obesity, and metabolic syndrome. Its AMPK-activating properties and effects on glucose and lipid metabolism make it a valuable tool for metabolic pathway research.

Mitochondrial Biology

As one of the first identified mitochondrial-derived peptides with systemic signaling functions, MOTS-C is a fundamental research tool in mitochondrial biology. It is used to study mito-nuclear communication, mitochondrial retrograde signaling, and the role of the mitochondrial genome in cellular regulation.

Exercise Physiology Research

MOTS-C’s exercise-mimetic properties make it a research target in exercise physiology, studying the molecular mechanisms by which physical activity produces metabolic benefits and whether these pathways can be pharmacologically activated.

Stress Biology and Resilience Research

MOTS-C’s role in cellular stress resistance positions it as a research compound for understanding adaptive stress responses, hormesis, and the molecular basis of resilience to metabolic and oxidative challenges.

Available Formats and Bulk Options

• Standard Research Vials: 5 mg lyophilized powder per vial
• High-Volume Vials: 10 mg per vial
• Bulk Lyophilized Powder: 50 mg, 100 mg, 500 mg quantities
• Custom Formulations: Available upon request

Wholesale Pricing Summary

For detailed pricing, visit our wholesale pricing page or contact our B2B team.

Quality, Testing, and Certificates of Analysis

• HPLC Purity: RP-HPLC confirms ≥99% purity.
• Mass Spectrometry: ESI-MS confirms molecular weight of 1787.0 g/mol.
• Amino Acid Analysis: Verifies correct 16-residue sequence MRWQEMGYIFYPRKLR.
• Endotoxin Testing: LAL assay <1 EU/mg.
• Sterility Testing: Per USP standards for in vivo presentations.
• Methionine Oxidation: Monitored and controlled below specified limits.

Storage and Stability

Lyophilized Form

• Long-term: -20°C, desiccated, protected from light. Shelf life 24+ months.
• Short-term: 2-8°C for up to 2 months.
• Note: MOTS-C contains two methionine residues susceptible to oxidation. Argon atmosphere packaging and desiccant storage are recommended.

Reconstituted Solution

• Vehicle: Sterile water or PBS. Avoid buffers with oxidizing agents.
• Storage: 2-8°C for up to 7 days; aliquot and freeze at -80°C for longer storage.

Compliance and Intended Use

Research Use Only (RUO). MOTS-C supplied by Wholesale Bulk Peptides is intended solely for in vitro and preclinical research. This product is not intended for human or veterinary diagnostic or therapeutic use. MOTS-C has not been approved by the FDA or any regulatory authority for any clinical application.

Purchasers assume full responsibility for compliance with all applicable regulations.

Related Compounds

• NAD+ — A coenzyme central to mitochondrial function and energy metabolism, frequently studied alongside MOTS-C in longevity research.
• GHK-Cu — A copper tripeptide studied in tissue repair and anti-aging research contexts.
• BPC-157 — A cytoprotective peptide studied in tissue repair models.

References

1. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. PMID: 25738459
2. Kim SJ, Mehta HH, Wan J, et al. Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging. 2018;10(6):1239-1256. PMID: 29886458
3. 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. Nat Commun. 2021;12(1):470. PMID: 33473109
4. 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 Metab. 2018;28(3):516-524. PMID: 30197299
5. D’Souza RF, Woodhead JST, Zeng N, et al. Circulatory exosomal miRNA following intense exercise is unrelated to muscle and plasma miRNA abundances. Am J Physiol Endocrinol Metab. 2018;315(4):E723-E733. PMID: 29969315

Frequently Asked Questions

What is MOTS-C?

MOTS-C is a 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene of mitochondrial DNA. Discovered in 2015 at USC, it functions as a systemic metabolic regulator with effects on glucose homeostasis, stress resistance, and cellular energy balance.

How was MOTS-C discovered?

MOTS-C was discovered by Changhan Lee and Pinchas Cohen at the University of Southern California in 2015 through bioinformatic analysis of short open reading frames within mitochondrial DNA, revealing previously unrecognized bioactive peptides encoded in mitochondrial rRNA genes.

What purity is guaranteed?

All MOTS-C is supplied at 99%+ purity by RP-HPLC with MS identity confirmation, amino acid analysis, endotoxin testing, and methionine oxidation monitoring on every batch.

Why is methionine oxidation a concern?

MOTS-C contains two methionine residues (positions 1 and 6) that are susceptible to oxidation, which can reduce biological activity. We monitor methionine oxidation levels and use argon atmosphere packaging to minimize oxidative degradation.

How should MOTS-C be stored?

Lyophilized at -20C desiccated and light-protected (24+ months stability). Reconstituted at 2-8C for 7 days maximum, or aliquot and store at -80C for longer periods. The methionine content makes MOTS-C more sensitive to oxidation than many peptides.

What is the minimum order quantity?

Wholesale orders start at 10 vials (5 mg each). Volume discounts range from 12% to 45%. Custom pricing for orders exceeding 1,000 vials.

Do MOTS-C levels change with age?

Research has shown that circulating MOTS-C levels decline with age in humans, correlating with age-related declines in mitochondrial function, metabolic capacity, and exercise performance. This age-dependent decline is a central research focus in the longevity field.

Is MOTS-C an exercise mimetic?

Research supports MOTS-C as an exercise-mimetic peptide. Physical exercise increases circulating MOTS-C levels, and exogenous MOTS-C activates many of the same metabolic pathways as exercise, including AMPK activation, enhanced glucose uptake, and improved fatty acid oxidation.

Is MOTS-C approved for human use?

No. MOTS-C is a Research Use Only compound. It has not been approved by the FDA or any regulatory authority for human or veterinary use.

What research areas use MOTS-C?

Aging/longevity, metabolic disease, mitochondrial biology, exercise physiology, stress biology, and cellular senescence research. It is a key tool for studying mitochondrial-derived peptide signaling.

What documentation is included?

Batch-specific COA with HPLC purity, MS identity, amino acid analysis, endotoxin, methionine oxidation levels, and appearance data. SDS available upon request.

How is MOTS-C shipped?

Lyophilized MOTS-C ships at ambient temperature in sealed, argon-atmosphere vials with desiccant. Cold-chain shipping is available upon request. Standard domestic delivery is 1-3 business days.