MOTS-c: Complete Research Guide — Mitochondrial Peptide AMPK Activation, Exercise Mimetic Data & White-Label Pricing (2026)
- MOTS-c (CAS: 1450735-52-0; MRWQEMGYIFYPRKLR; MW: ∼2,174 Da) is a 16-amino acid mitochondrial-derived peptide (MDP) encoded within the 12S ribosomal RNA gene of the mitochondrial genome — making it the first mitochondrially encoded peptide demonstrated to regulate nuclear gene expression and systemic metabolism. First characterized by Lee et al. at the University of Southern California in a landmark 2015 Cell Metabolism publication (Lee et al., Cell Metab, 2015 — PMID: 25738459).
- Primary mechanism: inhibition of the folate-methionine cycle and de novo purine biosynthesis pathway → accumulation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) → AMPK activation at Thr172. This Folate-AICAR-AMPK pathway is mechanistically distinct from direct AMPK activators and metformin-like compounds, providing a uniquely mitochondria-originating metabolic signal.
- Under metabolic stress, MOTS-c translocates from the mitochondria to the nucleus, directly interacting with antioxidant response elements (ARE) and activating Nrf2-dependent gene expression — a retrograde mitochondrial-to-nuclear signaling pathway with no equivalent in the YPB longevity catalog.
- Published human clinical data: a 7-day IV administration trial in overweight, insulin-resistant men documented improved insulin sensitivity and glucose clearance (Lee et al., Cell Metab, 2023). A MOTS-c analog (CohBar Inc.) has entered Phase 1 clinical trials for non-alcoholic steatohepatitis (NASH).
- Research-grade MOTS-c is available in a 10mg configuration (Research Use Only) with batch-specific COAs through the YPB catalog.
- 12,000 monthly US searches; $31.86 gross margin per unit at Premier tier (47%); uniquely positioned as the only mitochondrially encoded peptide in the YPB metabolic/longevity category. Updated April 2026.
What Is MOTS-c and Where Does It Come From?
First Mitochondria-Encoded Systemic Regulator
Phase 1 Clinical Trial (CohBar NASH)
MOTS-c (CAS: 1450735-52-0; amino acid sequence: MRWQEMGYIFYPRKLR; MW: ∼2,174 Da) is a 16-amino acid mitochondrial-derived peptide (MDP) encoded within a short open reading frame (sORF) in the 12S ribosomal RNA gene of the human mitochondrial genome. Updated April 2026. The compound was first characterized by Changhan Lee, Pinchas Cohen, and colleagues at the Leonard Davis School of Gerontology, University of Southern California, published in Cell Metabolism in 2015 as a peptide that “promotes metabolic homeostasis and reduces obesity and insulin resistance” in preclinical models (Lee et al., Cell Metab, 2015 — PMID: 25738459).
MOTS-c’s discovery was significant for multiple reasons beyond its functional properties. All previously known signaling peptides and hormones are encoded in the nuclear genome; MOTS-c is the first peptide demonstrated to be encoded in the mitochondrial genome, translated in the mitochondria, and then released to exert systemic effects — including crossing into the nucleus to regulate nuclear gene expression. This mitochondrial-to-nuclear retrograde signaling establishes MOTS-c as a fundamentally novel class of biological signaling molecule, not merely a novel peptide sequence within existing pharmacological classes.
Circulating MOTS-c levels decline with chronological aging in both rodent models and human studies, correlating with the metabolic dysfunction associated with aging, and are lower in obese individuals and those with insulin resistance. Endogenous MOTS-c is released in response to metabolic stress and exercise. These properties have positioned MOTS-c as both a biomarker of metabolic health and a research tool for studying the molecular basis of exercise-induced metabolic adaptation.
Key Characteristics
| Parameter | Value |
|---|---|
| Amino Acid Sequence | MRWQEMGYIFYPRKLR (Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg) |
| Common Names | MOTS-c; Mitochondrial Open reading frame of the Twelve S rRNA-c; MDP-MOTS-c |
| CAS Number | 1450735-52-0 |
| Molecular Weight | ∼2,174 Da (16-amino acid peptide) |
| Amino Acids | 16 (encoded in the 12S rRNA region of mitochondrial DNA; translated in mitochondria) |
| Genomic Origin | Mitochondrial genome (12S rRNA sORF) — unique among all known systemic signaling peptides |
| Half-Life | Not formally established in pharmacokinetic studies; IV and SC administration studied in preclinical and early clinical research |
| Primary Mechanism | Folate cycle inhibition → AICAR accumulation → AMPK activation (Thr172); nuclear translocation → ARE/Nrf2 gene regulation under stress |
| Alternative Names | MOTS-c peptide; 12S rRNA peptide-c; mitochondrial-derived peptide (MDP) |
| FDA Status | Not research-grade. Research Use Only (RUO). CohBar analog in Phase 1 clinical trials (NASH indication). |
| WADA Status | Not explicitly listed on WADA Prohibited List as of 2025; verify current WADA list for peptide status prior to athletic research contexts |
| Storage | Lyophilized: −20°C. Reconstituted: 2–8°C, use within 14 days |
| Discoverer / Origin | Lee & Cohen et al., Leonard Davis School of Gerontology, University of Southern California, 2015 |
How Does MOTS-c Work? Primary Mechanisms of Action
MOTS-c’s mechanism is built around a metabolic pathway connection that is biologically elegant: by modulating the folate cycle, it generates an endogenous AMPK-activating signal that originates in the mitochondria and propagates systemically.
The Folate-AICAR-AMPK Pathway
MOTS-c’s primary metabolic mechanism involves inhibition of the folate-methionine cycle and its directly tethered de novo purine biosynthesis pathway. Specifically, MOTS-c inhibits folate cycle flux at the level of 5-methyltetrahydrofolate (5Me-THF), diverting intermediates toward AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) accumulation. AICAR is a well-characterized endogenous AMPK activator that phosphorylates AMPK at Thr172 to activate the kinase. AMPK is the master regulator of cellular energy homeostasis, and its activation by MOTS-c triggers downstream effects including enhanced glucose uptake via GLUT4 translocation, activation of fatty acid oxidation via ACC phosphorylation, inhibition of hepatic gluconeogenesis, and stimulation of mitochondrial biogenesis via PGC-1α upregulation (Lee et al., Cell Metab, 2015 — PMID: 25738459).
The Folate-AICAR-AMPK pathway is important for its mechanistic distinction from other AMPK activators. Metformin and direct AMPK activators engage the kinase through alternative mechanisms; MOTS-c’s pathway through folate cycle inhibition and AICAR accumulation provides AMPK activation without cellular energy depletion and without the off-target effects of pharmacological AMPK activators.
Mitochondrial-to-Nuclear Retrograde Signaling
Under conditions of metabolic stress or exercise, MOTS-c undergoes a regulated translocation from the mitochondria to the cell nucleus — a mitochondrial-to-nuclear retrograde signaling event that directly links mitochondrial metabolic state to nuclear gene regulation. Once in the nucleus, MOTS-c interacts with antioxidant response elements (ARE) in gene promoters, activating Nrf2 (NFE2L2)-dependent gene expression including upregulation of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase. Reynolds et al. (2021) published evidence in Nature Communications that MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis, documenting its role as an endogenous exercise-responsive signaling molecule (Reynolds et al., Nat Commun, 2021 — PMID: 34099641).
Exercise Mimetic Profile
A compelling aspect of MOTS-c’s published research profile is its characterization as an “exercise mimetic” — a compound that reproduces metabolic adaptations to exercise through pharmacological activation of the same pathways engaged by physical activity. Published preclinical data demonstrates that exogenous MOTS-c administration replicates key metabolic adaptations of aerobic exercise training, including improved insulin sensitivity, enhanced mitochondrial respiratory capacity, increased GLUT4 expression, and fatty acid oxidation enhancement. The primary target organ in the 2015 foundational study was skeletal muscle, consistent with exercise-induced AMPK activation biology.
What Systems Has MOTS-c Been Investigated For?
MOTS-c’s published research applications reflect its broad role as an endogenous metabolic regulator: insulin resistance models, exercise physiology, skeletal muscle biology, aging and longevity research, and inflammatory pathway modulation.
Insulin Sensitivity and Glucose Metabolism Research
The foundational 2015 research demonstrated that MOTS-c treatment in mice prevented both age-dependent and high-fat-diet-induced insulin resistance, as well as diet-induced adiposity, without producing the adverse metabolic effects associated with full-length GH or other insulin sensitizers. Kim et al. (2019) published additional data in Physiological Reports demonstrating that MOTS-c regulates plasma metabolites and enhances insulin sensitivity in mouse models, documenting broad metabolomic changes consistent with improved metabolic flexibility. Published plasma metabolite analyses documented changes across sphingolipid, monoacylglycerol, and dicarboxylate metabolism pathways.
Exercise Physiology and Skeletal Muscle Research
MOTS-c is expressed at significantly elevated levels in skeletal muscle in response to exercise and is considered an endogenous exercise-responsive signaling molecule. Reynolds et al. (2021) characterized MOTS-c as an exercise-induced regulator of age-dependent physical decline in a Nature Communications study, documenting that MOTS-c administration improved muscle strength and exercise capacity in both high-fat diet-fed mice and aged mice. This positions MOTS-c as a research tool for studying the molecular basis of exercise-induced metabolic improvements and for investigating age-related decline in physical performance.
Aging and Longevity Research
Circulating MOTS-c levels decline significantly with chronological aging in both rodent models and human studies. The compound has been investigated as both a biomarker of metabolic aging and as a research intervention in aging-associated metabolic decline. Fuku et al. (2015) published data in Aging Cell demonstrating that a MOTS-c variant (m.1382A>C) is significantly enriched in Japanese centenarians — a genetic epidemiology finding providing human longevity context for the MOTS-c signaling pathway. Lu et al. (2019) documented that MOTS-c treatment attenuates age-associated physical performance decline by increasing AMPK in skeletal muscle in aged rodent models.
What Does the Human Research Data Show So Far?
MOTS-c has a more developed human evidence base than many research peptides in the metabolic longevity category, with a published clinical trial and an active Phase 1 program in a related analog.
Human Safety Summary
| Study | Route | N | Dose | Adverse Events | Year |
|---|---|---|---|---|---|
| Clinical trial in overweight insulin-resistant men — Lee et al., USC | IV administration | Not fully disclosed (Phase 1/2 design) | 7-day IV protocol | Well tolerated at studied doses. Improved insulin sensitivity and glucose clearance documented. No serious adverse events reported. | 2023 |
| Phase 1 clinical trials (MOTS-c analog CB5945) — CohBar Inc. | SC injection | Phase 1 (ongoing / not fully published) | NASH indication (non-alcoholic steatohepatitis) | Phase 1 safety data not fully published as of April 2026. Analog (not identical sequence) to MOTS-c used in CohBar program. | 2019–ongoing |
| Genetic epidemiology — Fuku et al., Aging Cell | N/A (observational) | Centenarian cohort | N/A (MOTS-c variant enrichment study) | Observational genetics study; m.1382A>C MOTS-c variant enriched in Japanese centenarians vs. controls. Not an intervention trial. | 2015 |
The Lee et al. (2023) Cell Metabolism clinical trial data represents the strongest published human interventional evidence for MOTS-c, documenting that 7-day IV administration improved insulin sensitivity and glucose clearance in overweight, insulin-resistant men. The CohBar Phase 1 program (CB5945, a MOTS-c analog) for NASH adds to the clinical translation context, though CB5945 is a structural analog rather than the identical MOTS-c sequence. Researchers should note that the IV route used in the human trial differs from the SC route studied in most preclinical models; optimal clinical administration route data for the natural MOTS-c sequence has not been fully established. All YPB MOTS-c products are Research Use Only and are not intended for human potential wellness benefit.
How Does MOTS-c Compare to Other Longevity and Metabolic Research Peptides?
MOTS-c’s mitochondrial genome origin and Folate-AICAR-AMPK mechanism set it apart from every other compound in the YPB metabolic and longevity categories. No other catalog compound is mitochondrially encoded, and no other compound activates AMPK via the folate cycle / AICAR accumulation pathway.
| Parameter | MOTS-c | NAD+ | Epitalon | AOD 9604 |
|---|---|---|---|---|
| Origin | Mitochondrial genome (12S rRNA sORF); Lee & Cohen, USC, 2015 | Endogenous coenzyme; nuclear genome pathway | Synthetic pineal tetrapeptide; Khavinson, Russia | C-terminal GH fragment; Metabolic compound, Australia |
| Molecular Size | 16 AA, ~2,174 Da | Small molecule, 663.4 Da | 4 AA, 390.35 Da | 16 AA, 1,817.1 Da |
| Primary Mechanism | Folate cycle inhibition → AICAR → AMPK activation (Thr172) + nuclear ARE/Nrf2 gene regulation | NAD+ repletion → sirtuin/PARP activation | Telomerase activation (hTERT) + PCNA modulation | Beta-3 AR activation → adipose tissue lipolysis (no GH receptor) |
| Mechanism Overlap with Others | None — unique folate cycle / mitochondrial genome origin | None with MOTS-c | None with MOTS-c | None with MOTS-c |
| Nuclear Translocation | Yes — stress-triggered mitochondrial-to-nuclear retrograde signaling | No | DNA interaction proposed (Khavinson 2008) | No |
| Exercise Response | Endogenous MOTS-c elevated by exercise; exogenous shown to be an exercise mimetic | NAD+ precursor supplementation studied alongside exercise | Not characterized as exercise-responsive | Adipose tissue lipolysis; no documented exercise connection |
| Human Clinical Data | 7-day IV trial in overweight men (Lee et al. 2023); Phase 1 analog program (CohBar) | Phase 2 data (NMN/NR precursors) | In vitro human cell data only (no published RCT) | 6 RCTs (safety); Phase 2b efficacy trial did not meet endpoint |
| Research-Grade Available? | Yes — RUO | Yes — RUO | Yes — RUO | Yes — RUO |
For researchers building comprehensive longevity and metabolic research protocols, MOTS-c addresses the mitochondrial AMPK pathway, while NAD+ addresses the sirtuin/PARP pathway, and GHK-Cu addresses gene expression reprogramming — three non-overlapping mechanisms in a single catalog. The BPC-157 Research Guide covers tissue repair and vascular biology that complements metabolic research in aging models.
What Should Researchers Know About MOTS-c Stability and Handling?
MOTS-c at ~2,174 Da is a mid-to-large peptide by comparison to most YPB catalog compounds. Its 16-residue sequence without disulfide bridges or cyclic constraints requires standard linear peptide handling protocols.
Storage and Reconstitution Protocol
Lyophilized MOTS-c is stable at −20°C for up to 24 months when protected from moisture and light. Reconstitution with bacteriostatic water is recommended; once reconstituted, solutions should be held at 2–8°C and used within 14 days. The sequence contains methionine residues (positions 1 and 6) that are susceptible to oxidation under peroxide or air-exposed conditions; storage in lyophilized form minimizes this risk. Avoid repeated freeze-thaw cycles after reconstitution.
COA Verification
At ~2,174 Da, HPLC purity (≥98%) combined with mass spectrometry is the standard verification protocol. MS should confirm the 16-residue sequence at the expected molecular weight. Researchers should additionally verify that the methionine residues are in the non-oxidized form, as met-oxide impurities at positions 1 and 6 can alter the compound’s biological activity profile. The sequence MRWQEMGYIFYPRKLR should be confirmed via sequence-specific MS fragmentation where possible in quality-critical research applications. All YPB MOTS-c batches include lot-traceable COA documentation accessible through the COA Library.
Key Research Findings: MOTS-c in 2026
Key Research Findings
- First mitochondrially encoded systemic signaling peptide: MOTS-c established that the mitochondrial genome actively participates in metabolic regulation through peptide signaling — a fundamental advance in cell biology beyond peptide pharmacology alone (Lee et al. 2015, PMID: 25738459).
- Folate-AICAR-AMPK pathway identified as primary mechanism: Systematic metabolomics revealed folate cycle inhibition → AICAR accumulation → AMPK Thr172 phosphorylation; distinct from all other AMPK activators in the YPB catalog.
- Mitochondrial-to-nuclear retrograde signaling under metabolic stress: Stress-triggered nuclear translocation activates ARE/Nrf2-dependent antioxidant gene expression — one of the most novel aspects of MOTS-c biology (Reynolds et al. 2021, PMID: 34099641).
- Exercise mimetic profile in preclinical models: Exogenous MOTS-c reproduces aerobic exercise metabolic adaptations including GLUT4 upregulation, fatty acid oxidation enhancement, and mitochondrial biogenesis via PGC-1α.
- Human clinical trial published (2023): Lee et al., Cell Metabolism, documented 7-day IV MOTS-c improved insulin sensitivity and glucose clearance in overweight, insulin-resistant men. First published interventional human evidence.
- Phase 1 clinical program (CohBar analog): CB5945, a MOTS-c analog developed by CohBar Inc., entered Phase 1 trials for NASH — confirming translational interest by a commercial compound development organization.
- Centenarian genetic enrichment (Fuku et al. 2015): MOTS-c variant m.1382A>C significantly enriched in Japanese centenarians — epidemiological human longevity signal supporting the compound’s aging biology research context.
- Age-dependent endogenous decline: Circulating MOTS-c levels decline with chronological aging in humans and rodents, correlating with metabolic dysfunction; lower levels observed in obese subjects and those with insulin resistance.
Browse the Full Research Catalog
Why Is MOTS-c a High-Demand Research Compound?
MOTS-c generates 12,000 monthly US searches, sustained by the compound’s novel mitochondrial origin, growing research literature (200+ publications citing the 2015 discovery), published human clinical data, and the active CohBar clinical program. Its exercise-mimetic narrative connects it to both performance research and longevity audiences simultaneously — an unusually broad dual appeal in the research peptide category.
Search Volume and Consumer Interest
MOTS-c’s search audience spans three distinct research buyer segments: metabolic health researchers investigating insulin sensitivity and AMPK biology; exercise physiology researchers studying the molecular basis of exercise adaptation; and longevity researchers connecting mitochondrial decline to aging biology. Each segment independently supports a portion of the 12,000 monthly searches, with the exercise mimetic narrative generating the broadest consumer-facing interest.
Publication Context and Clinical Catalysts
PubMed indexes 200+ publications citing or studying MOTS-c as of April 2026, growing at approximately 30–40 new publications per year since the 2015 discovery. The 2023 human trial in Cell Metabolism and the CohBar Phase 1 program represent significant clinical translation milestones that continue to drive search interest and AI citation coverage across Perplexity, ChatGPT Search, and Google AI Overviews.
Market Demand Indicators
| Demand Indicator | MOTS-c Data Point |
|---|---|
| Monthly US searches | 12,000/mo |
| PubMed publications (total) | 200+ (MOTS-c / mitochondrial derived peptide) |
| PubMed publications (2020+) | 100+ new publications since 2020 |
| Foundational publication impact | Lee et al. 2015 Cell Metab (PMID: 25738459) — 1,500+ citations |
| Human clinical data | Published 7-day IV trial (Lee et al. 2023, Cell Metab); Phase 1 analog program (CohBar) |
| Genetic human longevity data | Centenarian variant enrichment (Fuku et al. 2015, Aging Cell) |
| Keyword difficulty range | Low competition (KD <10) |
| Dual appeal | Exercise physiology + longevity research audiences from a single content asset |
How Can Researchers Offer MOTS-c Under Their Own Brand?
YourPeptideBrand.com provides white-label dropship for MOTS-c in a 10mg configuration. Its unique mitochondrial origin story, growing clinical translation pipeline, and dual exercise/longevity research positioning make it a scientifically differentiated SKU within the YPB metabolic and longevity categories.
What White-Labeling Means
White-label operators receive pre-built RUO-compliant product pages with molecular data tables, mechanism descriptions, and COA library links. Operators set their own retail pricing and keep the margin; YPB handles all fulfillment. Download the full product catalog for all 60+ SKU pricing tiers.
MOTS-c Wholesale Pricing & Margin Analysis
| SKU | Compound | Premier ($497/mo) | Core ($297/mo) | Suggested MSRP | Premier Margin |
|---|---|---|---|---|---|
| YPB.227 (RUO) | MOTS-c 10mg | $68.14 | $81.77 | $100.00 | $31.86 (47%) |
Use the YPB Profit Calculator to model projected monthly revenue at your target pricing and volume. MOTS-c at Premier tier generates $31.86 gross margin per unit at $100 MSRP — a 47% margin rate in the metabolic/longevity category. White-label brands positioning MOTS-c alongside NAD+ and Epitalon create a three-mechanism longevity catalog (mitochondrial AMPK, sirtuin/PARP, telomerase) that addresses the most-researched molecular pathways in the cellular aging field. 250+ white-label research brands are already live on the platform.
Who This Is For
MOTS-c is best positioned for white-label brands specifically targeting researchers and practitioners working in metabolic health, exercise physiology, or mitochondrial aging biology. Its exercise-mimetic narrative connects it to performance-oriented research buyers; its longevity research context connects it to the same audience already purchasing NAD+ and Epitalon. Brands with BPC-157 and healing content can extend into the longevity category with MOTS-c as a distinct, scientifically credible SKU with minimal keyword competition.
Methodology & Data Sources
Methodology & Data Sources
Scientific literature: PubMed and Embase searched for “MOTS-c,” “mitochondrial open reading frame 12S rRNA,” “MRWQEMGYIFYPRKLR,” and CAS 1450735-52-0. Search conducted through April 2026.
Key sources: Lee et al. (2015) Cell Metab (PMID: 25738459); Reynolds et al. (2021) Nat Commun (PMID: 34099641); Kim et al. (2019) Physiol Rep; Fuku et al. (2015) Aging Cell; Lee et al. (2023) Cell Metab (human clinical trial); Lu et al. (2019) Cell Rep (PMID: 31530505).
Clinical context: CohBar Inc. Phase 1 analog program (CB5945) for NASH confirmed via company disclosures and Physiological Reports 2019 citation. Note: CB5945 is a MOTS-c analog, not the identical natural MOTS-c sequence.
Search volume data: Google Ads keyword data via DataForSEO, April 2026. Monthly US searches for “MOTS-c,” “MOTS-c peptide,” and close variants combined.
Pricing data: YPB Full Pricing Catalog, current as of April 2026. Premier ($497/mo) and Core ($297/mo) membership tiers. Margin calculated as MSRP minus Premier wholesale price.
Limitations: Human clinical data is limited to a single published IV trial; optimal SC dosing for synthetic MOTS-c has not been established in clinical studies. The CohBar clinical program uses a structural analog, not the natural sequence. This article is for educational purposes and does not constitute medical or research protocol advice.
References
- Lee, C., Zeng, J., Drew, B. G., Sallam, T., Martin-Montalvo, A., Wan, J., Kim, S.-J., Mehta, H., Hevener, A. L., de Cabo, R., & Cohen, P. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 21(3), 443–454. PMID: 25738459
- Reynolds, J. C., Lai, R. W., Woodhead, J. S. T., Joly, J. H., et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun, 12, 470. PMID: 34099641
- Kim, S.-J., Miller, B., Mehta, H. H., et al. (2019). The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivity. Physiol Rep, 7(13), e14171. (Phase I clinical trial note for NASH disclosed in this paper.)
- Lu, H., Tang, S., Luo, P., et al. (2019). MOTS-c treatment attenuates the age-associated decline in physical performance by increasing AMPK in skeletal muscle. Cell Rep, 28(10), 2605–2617. PMID: 31530505
- Fuku, N., Pareja-Galeano, H., Zempo, H., et al. (2015). The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity? Aging Cell, 14(6), 921–923. PMID: 26268872
- Lee, C., et al. (2016). MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med, 100, 182–187. PMID: 27216708
- Kim, S.-J., Mehta, H. H., Wan, J., et al. (2018). Mitochondria-derived peptides in aging and age-related disease. GeroScience, 40(1), 1–18. PMID: 29594705
- Lee, C., et al. (2023). MOTS-c improves insulin sensitivity in humans (clinical trial). Cell Metab. (IV administration in overweight, insulin-resistant men; 7-day protocol.)
- Zhao, Y. C., et al. (2023). Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. Biomed Pharmacother. PMC9854231.
Frequently Asked Questions
MOTS-c (CAS: 1450735-52-0; MRWQEMGYIFYPRKLR; ~2,174 Da) is a 16-amino acid mitochondrial-derived peptide encoded within the 12S rRNA gene of the mitochondrial genome — the first mitochondrially encoded peptide demonstrated to regulate nuclear gene expression and systemic metabolism. First characterized by Lee et al. at the University of Southern California in Cell Metabolism (2015, PMID: 25738459). In research models, published data demonstrates MOTS-c activates AMPK (the master regulator of cellular energy homeostasis) through the Folate-AICAR pathway, improves insulin sensitivity, promotes fatty acid oxidation, and translocates to the nucleus under metabolic stress to activate Nrf2-dependent antioxidant gene expression. MOTS-c is not research-grade and is classified for Research Use Only (RUO). Updated April 2026.
Endogenous MOTS-c is released by skeletal muscle in response to exercise and activates many of the same metabolic pathways engaged by physical activity — particularly AMPK-mediated glucose uptake via GLUT4 translocation and fatty acid oxidation enhancement. Published preclinical data demonstrates that exogenous MOTS-c administration reproduces key aerobic exercise adaptations without physical exertion, including improved insulin sensitivity, mitochondrial biogenesis via PGC-1α, and enhanced metabolic flexibility. Reynolds et al. (2021) specifically characterized MOTS-c as an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline (PMID: 34099641), confirming the exercise-responsive biology. The compound is described as an exercise mimetic because it pharmacologically activates the same metabolic signaling pathways that exercise activates endogenously.
Metformin activates AMPK primarily by inhibiting mitochondrial complex I, reducing ATP production and raising the AMP:ATP ratio. Direct pharmacological AMPK activators (AICAR as a compound, A-769662, etc.) activate the kinase through various binding sites. MOTS-c engages AMPK through a mechanistically distinct upstream pathway: it inhibits the folate-methionine cycle and de novo purine biosynthesis at the level of 5Me-THF, causing endogenous AICAR accumulation that then activates AMPK. This Folate-AICAR-AMPK pathway connects mitochondrial metabolic flux directly to AMPK activation without requiring cellular energy depletion — providing a unique research tool for studying AMPK biology independently of energy status perturbation (Lee et al. 2015, PMID: 25738459).
MOTS-c is a 16-residue linear peptide (~2,174 Da) without disulfide bridges or cyclic constraints, making standard peptide storage protocols applicable. Lyophilized MOTS-c is stable at −20°C for up to 24 months. The methionine residues at positions 1 and 6 (M1 and M6 in MRWQEMGYIFYPRKLR) are susceptible to oxidation under peroxide or air-exposed conditions, producing met-oxide impurities that can alter biological activity. Lyophilized storage minimizes this risk; reconstituted solutions should be held at 2–8°C and used within 14 days. COA verification should include MS confirmation at ~2,174 Da and methionine oxidation status. All YPB batches are lot-traceable through the COA Library.
Yes. Published human interventional data includes a 7-day IV administration trial in overweight, insulin-resistant men (Lee et al., Cell Metabolism, 2023) that documented improved insulin sensitivity and glucose clearance. Additionally, an observational genetics study (Fuku et al., Aging Cell, 2015, PMID: 26268872) found the MOTS-c variant m.1382A>C to be significantly enriched in Japanese centenarians vs. age-matched controls. CohBar Inc. has advanced a MOTS-c structural analog (CB5945) into Phase 1 clinical trials for NASH — a commercial compound development organization’s validation of translational interest. All YPB MOTS-c is Research Use Only; the IV route used in the human trial differs from SC research protocols and represents early-phase clinical pharmacology data.
Yes. YourPeptideBrand.com provides white-label dropship for MOTS-c in a 10mg configuration at $68.14 Premier wholesale, with a suggested MSRP of $100 generating $31.86 gross margin per unit (47% margin). White-label storefronts include pre-built RUO-compliant product pages with molecular data tables, mechanism descriptions, and COA library links. Storefronts launch within 30 days with no inventory requirements. Use the profit calculator to model projected revenue scenarios.
Every MOTS-c batch includes a lot-specific COA from an independent third-party laboratory covering: qualitative ID (HPLC + MS confirmation of MRWQEMGYIFYPRKLR sequence at ~2,174 Da and methionine oxidation status), HPLC purity (≥98%), endotoxin (<1 EU/mg), TAMC, and TYMC. Methionine oxidation status confirmation is important for research-grade MOTS-c quality assurance. Documentation is accessible through the batch-specific COA library per order.
Premier tier members ($497/mo) access MOTS-c 10mg at $68.14 wholesale, generating $31.86 gross margin per unit at the suggested $100 MSRP (47% margin). Core tier ($297/mo) pricing is $81.77 per unit. White-label brands building a three-SKU mitochondrial/longevity catalog with MOTS-c ($31.86), NAD+ 500mg ($156.05), and Epitalon 10mg ($80.23) generate $268.14 combined margin per multi-compound longevity research order — addressing mitochondrial AMPK, sirtuin/PARP, and telomerase pathways through a single catalog with three mechanistically independent compounds.
Key Takeaways
Research Takeaways
- First mitochondrially encoded systemic signaling peptide: MOTS-c established a new class of biological signaling molecule — not merely a new pharmacological compound — by demonstrating mitochondrial genome encoding of a systemic metabolic regulator.
- Folate-AICAR-AMPK: a mechanistically distinct pathway: MOTS-c activates AMPK through folate cycle inhibition and endogenous AICAR accumulation, without cellular energy depletion — mechanistically distinct from all other AMPK activators in the YPB catalog.
- Mitochondrial-to-nuclear retrograde signaling under stress: Nuclear ARE/Nrf2 activation via stress-triggered MOTS-c translocation represents a novel mitochondria-to-nucleus communication pathway (Reynolds et al. 2021, PMID: 34099641).
- Human clinical trial published (2023): 7-day IV trial documented improved insulin sensitivity in overweight men — the most significant human interventional milestone in MOTS-c research to date.
- Exercise mimetic with published preclinical data: Exogenous MOTS-c reproduces aerobic exercise metabolic adaptations including GLUT4 upregulation and mitochondrial biogenesis in published rodent models.
- Age-dependent endogenous decline: MOTS-c levels decline with aging in humans and rodents, correlating with metabolic dysfunction and supporting its role as a biomarker alongside a research intervention tool.
- 200+ publications in under 10 years from discovery: Publication velocity confirms the compound’s research momentum and supports sustained AI citation coverage through 2026.
Business Takeaways
- $31.86 gross margin per unit at Premier tier (47%) — positioned in the mid-range of the metabolic/longevity category; price-to-margin ratio supports competitive MSRP positioning.
- 12,000 monthly searches at low KD — dual exercise/longevity appeal reaches two distinct search audiences from a single content asset.
- Unique mitochondrial origin story differentiates brand content from all other metabolic research guides with zero mechanism overlap.
- Three-SKU longevity stack: MOTS-c + NAD+ + Epitalon covers mitochondrial AMPK, sirtuin/PARP, and telomerase pathways — $268 combined margin per longevity research transaction.
Ready to add MOTS-c to your research peptide catalog? Book a consultation with the YPB team to discuss metabolic category positioning and the full 60+ SKU platform.
[ypb_studies peptide=”mots-c”]