| Pack Size | Single Vial, 10-Pack |
|---|
MOTS-c is a synthetic 16-residue mitochondria-encoded peptide originally identified within an open reading frame of the human 12S ribosomal RNA gene. The compound has been studied across metabolic regulation, exercise-induced mitohormesis, and mitochondrial-respiration model systems, with the literature anchored by the 2015 Lee laboratory discovery paper and a rapidly expanding 2020s research record. Every Ronin batch is independently verified by Janoshik Analytical using HPLC for purity and mass spectrometry for identity, with the minimum acceptance threshold set at 99 percent purity by HPLC. The compound is supplied as a lyophilized powder in a sealed glass vial, 10 mg per vial. For laboratory research use only — not for human or veterinary use.
Description
MOTS-c is a synthetic 16-amino-acid peptide whose sequence is encoded within the mitochondrial DNA — specifically, an open reading frame located inside the 12S ribosomal RNA gene region. The compound's name expands as Mitochondrial Open reading frame of the 12S ribosomal RNA-c. Discovery of the peptide and its biological activity was reported in a 2015 paper from the Pinchas Cohen and Changhan Lee laboratory at the University of Southern California (PMID 25738459), and the molecule has since been characterised as one of the most extensively studied members of the broader mitochondrial-derived peptide (MDP) class.
The Lee laboratory's 2015 paper described that MOTS-c crosses from mitochondrion to cytoplasm and signals through AMP-activated protein kinase (AMPK), the master metabolic regulator of cellular energy balance. Subsequent work in 2018 documented that MOTS-c also translocates to the nucleus under metabolic stress and binds to specific transcription factors, exerting gene-regulatory effects in addition to its cytoplasmic AMPK signalling (PMID 29983246). The dual cytoplasm-and-nucleus mechanism distinguishes MOTS-c from many other peptide research compounds.
The compound is supplied as a lyophilized white-to-off-white powder in a sealed amber-glass vial under inert gas. Each vial contains 10 mg of peptide. Reconstitution with bacteriostatic water is required before the peptide can be drawn into an insulin syringe. Reconstitution mechanics are covered in the Reconstitution accordion below.
MOTS-c has been the subject of an expanding preclinical literature spanning metabolic regulation (PMID 27216708, PMID 34798268), exercise and mitohormesis (PMID 33535098, PMID 33722744), aging-related mitochondrial decline, neuroprotection (PMID 37285113), cardiovascular research (PMID 38008175, PMID 40661667), and cancer research (PMID 39321430). A 2023 review in Frontiers in Endocrinology compiled the broader research agenda around therapeutic exploitation of the compound (PMID 36761202). A 2026 review in Pathology Research and Practice extended the framing into cross-disease microprotein research, covering both cancer and neurodegeneration applications (PMID 41468641).
Across the literature the compound appears as MOTS-c, MOTSc, the formal Mitochondrial Open reading frame of the 12S rRNA-c, or under the broader category label "mitochondrial-derived peptide" or MDP. The compound is endogenous to humans and other mammals — the synthetic supply form replicates the sequence encoded within the human mitochondrial genome.
No regulatory authority — Health Canada, the FDA, the EMA, the TGA, or any equivalent — has cleared MOTS-c for therapeutic use in humans or animals. The compound has not progressed through a drug-approval pathway in any major jurisdiction. Ronin Peptides ships the compound exclusively as a research-grade reagent for benchwork. Dosing protocols, treatment regimens, and administration instructions are out of scope and not provided in any form.
Mechanism in research literature
The mechanistic anchor for MOTS-c is its activation of AMP-activated protein kinase, the master regulator of cellular energy balance. AMPK activation downstream of MOTS-c exposure has been characterised across multiple cell types including skeletal muscle myocytes, adipocytes, and hepatocytes. The 2015 Lee laboratory discovery paper documented that MOTS-c administration improved insulin sensitivity in diet-induced-obesity mouse models, with corresponding AMPK pathway activation observed in skeletal muscle and adipose tissue (PMID 25738459).
Beyond cytoplasmic AMPK signalling, MOTS-c has been characterised as a peptide that translocates to the nucleus under metabolic stress. A 2018 paper in Cell Metabolism documented that nuclear MOTS-c binds to the antioxidant response element and modulates transcription of nuclear-encoded genes related to mitochondrial function and stress response (PMID 29983246). The dual subcellular localisation broadens the compound's mechanism beyond a simple metabolic regulator into a regulator of nuclear-mitochondrial communication.
Folate and methionine pathway modulation has been characterised as a third mechanism stream. MOTS-c interacts with one-carbon metabolism through folate-cycle intermediate flux, providing an additional metabolic-regulatory route distinct from direct AMPK activation. The folate-pathway mechanism has been observed in vitro and in animal-model contexts, particularly in the metabolic-stress and exercise-response literature.
Exercise-induced mitohormesis is the fourth major mechanism stream. A 2021 paper in Cell Metabolism characterised that MOTS-c contributes to the hypothalamic POMC neuron response to regular exercise, with mitohormetic effects on neural energy balance (PMID 33535098). A 2021 paper in Biochimica et Biophysica Acta Molecular Basis of Disease documented synergistic regulation of PGC-1α expression — the master regulator of mitochondrial biogenesis — under combined MOTS-c and exercise intervention (PMID 33722744). A 2025 paper in Free Radical Biology and Medicine characterised that endurance training enhanced skeletal-muscle mitochondrial respiration through MOTS-c upregulation (PMID 39706498).
Recent literature has extended the mechanism work into Nrf2-dependent antioxidant signalling (PMID 38790718), tumour-suppression research in ovarian-cancer models (PMID 39321430), and stress-response research more broadly (PMID 36670507). The expanding mechanism picture positions MOTS-c at the intersection of metabolic regulation, mitochondrial-nuclear communication, and stress-response signalling.
Studied properties
Metabolic regulation forms the largest body of preclinical research on MOTS-c. The 2015 Lee laboratory paper described improvements in insulin sensitivity, glucose homeostasis, and energy expenditure in diet-induced-obesity mouse models (PMID 25738459). A 2016 follow-up paper in Free Radical Biology and Medicine extended the muscle-and-fat regulatory characterisation (PMID 27216708). A 2022 paper in Pharmacological Research documented that MOTS-c relieved hyperglycaemia and insulin resistance in additional model systems (PMID 34798268). The metabolic stream has produced the most consistent cross-laboratory replication of the early findings.
Exercise and mitohormesis research forms the second major stream. The combined MOTS-c-and-exercise findings position the compound as a candidate for research into exercise-mimetic mechanisms, with PGC-1α and mitochondrial biogenesis observed across multiple cell-type and tissue-level contexts (PMID 33722744, PMID 39706498). The 2021 Cell Metabolism paper on hypothalamic POMC neurons broadened the application bracket toward central-nervous-system contexts (PMID 33535098). The exercise stream connects mechanistically to the metabolic stream through shared AMPK and mitochondrial-biogenesis effectors.
Cardiovascular research has expanded into a dedicated stream. A 2024 review in Journal of Advanced Research compiled the broader mitochondrial-derived-peptide cardiovascular framings (PMID 38008175). A 2025 paper in Frontiers in Physiology characterised that MOTS-c restored mitochondrial respiration in type-2 diabetic heart tissue, framing one route by which the compound engages cardiac-metabolic disease research (PMID 40661667). The cardiac stream represents one of the more active translation tracks for the compound family.
Neuroprotection and neuropathic-pain research has emerged as a fourth stream. A 2023 paper in ACS Chemical Neuroscience characterised that MOTS-c ameliorated spared-nerve-injury-induced neuropathic pain in rodent models, framing the compound's potential application to peripheral-nerve research (PMID 37285113). The neuroprotection findings build on the broader metabolic and mitohormesis mechanism work, since neural tissue is energetically demanding and disproportionately affected by mitochondrial dysfunction.
Cancer research has produced a smaller but expanding stream. A 2024 paper in Advanced Science characterised that MOTS-c suppressed ovarian cancer progression through mitochondrial-mediated effects (PMID 39321430). A 2026 review in Pathology Research and Practice compiled the cross-disease microprotein research framings, covering both cancer-suppression and neurodegeneration applications under a unified mitochondrial-derived microprotein category (PMID 41468641). Researchers working in this stream should attend to the framing carefully — the cancer-research findings are mechanistic and preclinical, not therapeutic claims.
Translation to human clinical application remains limited. Despite the rapidly expanding preclinical literature and the foundational nature of the mitochondrial-derived peptide research field, no MOTS-c-based therapeutic has progressed to drug-approval-relevant clinical trials. The 2023 Frontiers in Endocrinology review described the compound as "promising for therapeutic exploitation" but framed the development pathway as still in early stages (PMID 36761202).
Compound specifications
| Specification | Value |
|---|---|
| Common name | MOTS-c |
| Alternate names | MOTSc; Mitochondrial Open reading frame of the 12S rRNA-c; mitochondrial-derived peptide MOTS-c |
| Molecular formula | C100H152N28O22S2 |
| Molecular weight | ~2174.55 g/mol (free acid form) |
| CAS number | 1627580-64-6 |
| Sequence (one-letter) | MRWQEMGYIFYPRKLR |
| Sequence (three-letter) | Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg |
| Length | 16 amino acids |
| Source gene | Mitochondrial 12S rRNA (MT-RNR1) open reading frame |
| Form | Lyophilized white-to-off-white powder |
| Solubility | Bacteriostatic water; sterile water for injection |
| Vial contents | 10 mg peptide, sealed amber-glass vial under inert gas |
| Purity | ≥99% by HPLC (verified per batch by Janoshik Analytical) |
Storage and handling
Unopened lyophilized vials hold up well under dry ambient storage; usable activity persists for several weeks even without refrigeration. The recommended container is the unopened original vial — keep the seal intact until reconstitution. Refrigeration at 2–8 °C is appropriate once the working timeline extends past a month. A standard freezer at −20 °C handles archival storage; ultra-low storage at −80 °C is rarely needed for typical bench-research timescales.
Keep vials shielded from light, ideally in their original outer packaging. Repeated temperature cycling accelerates degradation noticeably more than steady storage at any single temperature inside the recommended bands — minimise transitions between cold and ambient.
After reconstitution, refrigerate the solution at 2–8 °C without delay. The typical working window for a reconstituted preparation is four to six weeks at fridge temperature. Past that window, peptide concentration drifts downward through chemical degradation pathways even though the bacteriostatic water's benzyl alcohol still suppresses microbial growth. The 0.9% benzyl alcohol holds back bacterial contamination — the dominant spoilage path — but does not arrest the slower hydrolysis, oxidation, and aggregation processes that accumulate in any aqueous peptide solution.
When a research timeline extends past six weeks, common practice is splitting the reconstituted solution into single-use volumes and freezing them at −20 °C immediately. Ice-crystal formation during each freeze-thaw cycle inflicts mechanical damage on peptide chains, and pre-splitting eliminates the cumulative loss that comes from thawing one vial multiple times. Thaw individual aliquots overnight in a refrigerator — never at room temperature — and use them within a few days of thaw.
The reconstituted product should be visually clear and colourless. Discard any vial showing turbidity, suspended particulate, yellowing, or visible precipitate. The diluent of choice is USP-grade bacteriostatic water containing 0.9% benzyl alcohol — see the bacteriostatic water product page for reconstitution-grade water.
Compare with similar compounds
| Compound | Primary research area | Documented mechanism (preclinical) | Format at Ronin |
|---|---|---|---|
| MOTS-c | Metabolic regulation; mitohormesis; aging research | AMPK pathway activation; nuclear translocation; PGC-1α / mitochondrial biogenesis | 10 mg vial |
| Epitalon | Aging research; pineal-axis research | Telomerase modulation; pineal-tetrapeptide signalling | 10 mg vial |
| NAD+ | Cellular energy; sirtuin pathway | NAD+ co-factor restoration; sirtuin and PARP enzyme support | 500 mg vial |
| 5-Amino-1MQ | Metabolic regulation; NNMT inhibition | NNMT enzyme inhibition; methyl-donor pool research | 10 mg vial |
MOTS-c sits within the broader anti-aging and metabolic-research category at Ronin alongside Epitalon, NAD+, and 5-Amino-1MQ. The four compounds engage non-overlapping mechanisms — MOTS-c through AMPK and nuclear-mitochondrial communication, Epitalon through telomerase and pineal-axis signalling, NAD+ through co-factor restoration, and 5-Amino-1MQ through NNMT enzyme inhibition. Researchers planning multi-compound metabolic protocols sometimes examine MOTS-c alongside one of the others.
Reconstitution and laboratory handling
A 10 mg vial of MOTS-c reconstituted with 2 mL of bacteriostatic water yields a final concentration of 5 mg/mL, or 5,000 mcg/mL. Other diluent volumes scale linearly: 1 mL gives 10 mg/mL, 5 mL gives 2 mg/mL. The choice of reconstitution volume comes down to the working concentration the researcher wants to draw — there is no single "correct" volume.
Reconstitution procedure:
- Bring both vials — peptide and bacteriostatic water — to room temperature before opening.
- Sanitise both rubber stoppers with an alcohol swab.
- Pull the chosen diluent volume into a sterile transfer syringe.
- Direct the water against the inner wall of the peptide vial as it is injected — never onto the lyophilized cake, since direct impact foams the solution and denatures peptide at the air-water interface.
- Invert slowly or swirl gently until everything dissolves. Do not vortex; do not shake.
- Refrigerate at 2–8 °C the moment reconstitution completes.
A finished preparation should be visually transparent with no suspended particulate. If the solution is hazy or contains visible material, treat it as degraded or contaminated and discard.
For dose-volume calculations on insulin syringes, use the Ronin peptide reconstitution calculator. The calculator pre-loads MOTS-c with default reconstitution volumes and converts target doses to U-100 syringe units automatically.
In published preclinical research, MOTS-c has been administered at micrograms-to-milligrams-per-kilogram dose ranges in rodent metabolic and exercise model systems, with intraperitoneal and subcutaneous routes most common (PMID 25738459, PMID 33535098, PMID 39706498). Dose-response characterisation has been documented in cardiac and skeletal-muscle research contexts (PMID 40661667). These figures are research-reference only — Ronin Peptides does not provide dosing recommendations or administration instructions for any non-laboratory purpose.
Frequently asked questions
What is MOTS-c?
MOTS-c is a synthetic 16-residue peptide whose sequence is encoded within the mitochondrial DNA — specifically inside an open reading frame located in the 12S ribosomal RNA gene. It belongs to the mitochondrial-derived peptide (MDP) class of small peptides encoded within the mitochondrial genome. The compound was characterised in 2015 by the Lee laboratory at the University of Southern California. Research has investigated MOTS-c across metabolic regulation, exercise-induced mitohormesis, aging-related mitochondrial decline, neuroprotection, cardiovascular research, and cancer research streams. Ronin supplies the compound as a lyophilized vial reconstituted with bacteriostatic water at the bench. Sale is limited to laboratory research applications; human and veterinary use are excluded.
What does MOTS-c stand for?
MOTS-c expands as Mitochondrial Open reading frame of the 12S rRNA-c. The "c" suffix distinguishes this particular open reading frame from other potential mitochondrial-encoded peptides in the same broader category. The compound is encoded within the human mitochondrial genome, specifically within an open reading frame located inside the 12S ribosomal RNA gene (MT-RNR1). The synthetic supply form replicates the sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg, written in one-letter code as MRWQEMGYIFYPRKLR.
What is the regulatory status of MOTS-c?
No regulatory body — Health Canada, the FDA, the EMA, the TGA, or any equivalent — has approved MOTS-c as a drug for human or veterinary use. The compound has not progressed through a drug-approval pathway in any major jurisdiction, despite a rapidly expanding preclinical research literature.
MOTS-c is not listed as a scheduled controlled substance under the international drug-control conventions or under the major national scheduling systems. It sits within the regulatory layer covering laboratory reagents and research chemicals, not the layer governing human therapeutics.
Ronin Peptides supplies the compound as a research-grade reagent for laboratory and bench-research applications. Buyers operate under their own jurisdictional laws and any applicable institutional review protocols when handling the compound — Ronin Peptides assumes no oversight of downstream lab practice.
How is MOTS-c verified?
Each batch passes through Janoshik Analytical — an independent peptide-analytics lab — for HPLC purity quantification and MS identity confirmation, with the minimum acceptance threshold set at 99 percent purity by HPLC. Every Janoshik COA includes a verification key that resolves at janoshik.com, so researchers can confirm the certificate's authenticity without trusting the manufacturer's word alone. To pull the COA covering the batch on your order, email support@roninpeptides.ca from the address used at checkout, with your order number; the typical reply turnaround is well under 24 hours.
How is MOTS-c different from other peptides?
MOTS-c is one of a small class of mitochondrial-derived peptides (MDPs) — peptides encoded within the mitochondrial genome rather than the nuclear genome. This origin distinguishes MOTS-c from most other research peptides, which are encoded by nuclear genes. The compound's mechanism centres on AMPK pathway activation in the cytoplasm and gene-regulatory effects in the nucleus under metabolic stress. Other peptides in Ronin's anti-aging and metabolic categories — Epitalon, NAD+, 5-Amino-1MQ — engage non-overlapping mechanisms (telomerase, NAD+ co-factor restoration, NNMT enzyme inhibition respectively).
How is MOTS-c reconstituted?
The standard preparation is 2 mL of bacteriostatic water added to a 10 mg vial, producing a 5 mg/mL solution. Inject the water against the inside wall of the vial — never directly onto the lyophilized powder, which causes foaming and surface denaturation. Swirl gently or invert slowly until fully dissolved (typically 30–60 seconds). Refrigerate at 2–8 °C immediately after reconstitution. Use the Ronin reconstitution calculator for non-standard volumes or to convert target doses to insulin-syringe units.
How do I receive the COA for my batch?
Email support@roninpeptides.ca from the email address used at checkout, with your order number (e.g., RP-CA-1234) and the compound name. We reply within 24 hours — typically the same business day — with the COA PDF attached. The COA includes the Janoshik verification key, which you can check independently at janoshik.com to confirm the test results match what the laboratory ran on your specific batch. COAs are not published publicly to protect supply-chain privacy and prevent competitor scraping.
References
- Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis. Cell Metab. 2015;21(3):443-454. PMID: 25738459 | doi:10.1016/j.cmet.2015.02.009
- Lee C et al. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat. Free Radic Biol Med. 2016;100:182-187. PMID: 27216708 | doi:10.1016/j.freeradbiomed.2016.05.015
- Kim KH et al. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression. Cell Metab. 2018;28(3):516-524. PMID: 29983246 | doi:10.1016/j.cmet.2018.06.008
- Kang GM et al. Mitohormesis in Hypothalamic POMC Neurons Mediates Regular Exercise-Induced Energy Balance. Cell Metab. 2021;33(2):334-349. PMID: 33535098 | doi:10.1016/j.cmet.2021.01.003
- Yang B et al. MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression. Biochim Biophys Acta Mol Basis Dis. 2021;1867(6):166126. PMID: 33722744 | doi:10.1016/j.bbadis.2021.166126
- Yin Y et al. The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance. Pharmacol Res. 2022;175:105987. PMID: 34798268 | doi:10.1016/j.phrs.2021.105987
- Wan W et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress. J Transl Med. 2023;21:36. PMID: 36670507 | doi:10.1186/s12967-023-03885-2
- Zheng Y et al. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol. 2023;14:1120533. PMID: 36761202 | doi:10.3389/fendo.2023.1120533
- Jiang J et al. Mitochondrial-Derived Peptide MOTS-c Ameliorates Spared Nerve Injury-Induced Neuropathic Pain. ACS Chem Neurosci. 2023;14(8):1455-1465. PMID: 37285113 | doi:10.1021/acschemneuro.3c00140
- Li Y et al. Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities. J Adv Res. 2024;64:99-115. PMID: 38008175 | doi:10.1016/j.jare.2023.11.018
- Zhang Y et al. The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Pathway. Antioxidants. 2024;13(5):613. PMID: 38790718 | doi:10.3390/antiox13050613
- Yin Y et al. Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression. Adv Sci. 2024. PMID: 39321430 | doi:10.1002/advs.202405620
- Feng Y et al. Endurance training enhances skeletal muscle mitochondrial respiration by promoting MOTS-c. Free Radic Biol Med. 2025;226:1-11. PMID: 39706498 | doi:10.1016/j.freeradbiomed.2024.12.038
- Pham T et al. Mitochondria-derived peptide MOTS-c restores mitochondrial respiration in type 2 diabetic heart. Front Physiol. 2025;16:1602271. PMID: 40661667 | doi:10.3389/fphys.2025.1602271
- Hu S et al. Mitochondrial-derived microproteins in cancer and neurodegeneration. Pathol Res Pract. 2026;257:156344. PMID: 41468641 | doi:10.1016/j.prp.2025.156344
