MOTS-c: sourcing, documentation and price

MOTS-c — mitochondrial open reading frame of the 12S rRNA type-c, also written mitochondrial open-reading frame of the 12S rRNA-c — is a mitochondrial-derived peptide (MDP) encoded within the 12S rRNA region of mitochondrial DNA. It is classified as a mitokine and, per more recent work, as a mitochondrial-encoded host defense peptide (HDP) with amphipathic and cationic character [1]. The evidence block does not supply a CAS number, molecular formula or molecular weight for the peptide; the wild-type sequence given in the literature is Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg [4]. The m.1382A>C polymorphism in the MOTS-c gene is the variant most often genotyped in the studies below [7].

The work on this peptide centres on mitochondrial bioenergetics and on the NLRP3 inflammasome as an inflammatory node, with downstream readouts in insulin sensitivity, oxidative stress and cardiac tissue [2][3][5].

Research Studies

MOTS-c and antibacterial host defense

MOTS-c was identified as a peptide encoded in the human mitochondrial genome, presumably derived from primordial proto-mitochondrial bacteria, with direct antibacterial and immunomodulatory functions consistent with known host defense peptides. In that work the peptide targeted Escherichia coli [1]. This is the finding that reframes MOTS-c from a purely metabolic regulator to an immune effector, and it is the reason the peptide appears in immunology as well as metabolism literature.

MOTS-c and NLRP3 inflammasome activity in a diabetic rat model

In a high-fat diet and streptozotocin-induced type 2 diabetes rat model, MOTS-c treatment significantly reduced fasting blood glucose and circulating C-reactive protein, and selectively modulated plasma inflammatory mediators, with suppression of systemic and cardiac NLRP3 inflammasome activation [2]. The model is animal; the findings are not human data.

MOTS-c and circulating levels in Hashimoto's thyroiditis

A cross-sectional study compared 90 patients diagnosed with Hashimoto's thyroiditis against age- and sex-matched healthy controls and examined the association between circulating MOTS-c and thyroid autoimmunity and metabolic regulation [3]. The study is observational: it reports an association between circulating peptide levels and disease state, not a causal or therapeutic effect.

MOTS-c and LAT1-mediated delivery in radiation-induced lung injury

Wild-type MOTS-c is highly polar and shows poor membrane permeability. Substituting the arginine at position 13 with alanine produced R13A-MOTS-c, raising the hydrophobicity index from -0.938 to -0.544 and measurably improving cellular uptake. Competition assays with the canonical LAT1 substrates leucine and BCH, together with LAT1 knockdown, confirmed that R13A-MOTS-c enters cells via LAT1. In that setting the engineered peptide attenuated radiation-induced lung injury via Nrf2 activation and mitochondrial protection [4]. This is an engineered analogue, not the wild-type peptide, and the work is preclinical.

MOTS-c and atrial fibrillation in human tissue and mouse models

Human atrial tissue expression of humanin and MOTS-c was analysed using public GEO data, immunohistochemistry and immunofluorescence, and plasma levels were measured; therapeutic potential and mechanisms were then evaluated in an angiotensin II-induced mouse model and in primary cardiac cells. The reported effect was attenuation of atrial fibrillation by suppressing fibrosis and mitochondrial dysfunction [5]. The page should be read as a mixed human-observation plus animal-intervention study.

MOTS-c and myocardial ischemia-reperfusion injury in acute myocardial infarction

Seventy-two patients with acute myocardial infarction undergoing percutaneous coronary intervention were divided into MIRI (n = 34) and non-MIRI (n = 38) groups, and MOTS-c levels were measured in peripheral serum and intracoronary blood alongside clinical data [6]. This is a cross-sectional association study in a clinical population; it does not establish that altering MOTS-c levels changes reperfusion injury.

MOTS-c and polycystic ovary syndrome in adolescents

This study compared serum MOTS-c levels between adolescents diagnosed with PCOS and those without, assessed associations with metabolic parameters, and evaluated the relationship between the m.1382A>C polymorphism and serum levels [7]. The polymorphism had previously been linked to increased type 2 diabetes risk in men, which is why it is genotyped here.

MOTS-c and anesthetic technique in renal transplantation

A prospective controlled trial registered on ClinicalTrials.gov compares sevoflurane general anesthesia against combined spinal-epidural anesthesia in kidney transplant recipients, with ferroptosis, humanin and MOTS-c levels as endpoints, on the rationale that ischemia-reperfusion injury affects graft function and that these mitochondrial-derived peptides are thought to protect against oxidative stress [8]. This is a registered protocol; the evidence block does not report results.

MOTS-c in sepsis-induced cardiomyopathy and in human mesenchymal stromal cells

Two further lines of work sit behind the sections above. A review addresses MOTS-c in sepsis-induced cardiomyopathy, a cardiac complication of sepsis characterised by inflammatory dysregulation, mitochondrial dysfunction, metabolic disturbance and changes in the myocardial microenvironment [9]. Separately, work in human mesenchymal stromal cells reports that MOTS-c activates metabolic signalling but blunts reparative function, in a context where obesity compromises MSC metabolism and reparative capacity [10]. A further review discusses how a secreted mitochondrial microprotein may become a treatment for inflammatory lung diseases, noting intracrine, paracrine and endocrine effects across tissues [11], and a preclinical cardiac study reports that MOTS-c preserves mitochondrial subpopulation bioenergetics and genome integrity to attenuate ischemia-reperfusion injury [12].

What documentation a supplier should provide

Because the research record spans animal models, human cross-sectional cohorts and engineered analogues, batch documentation matters more than a marketing claim. A research-use supplier should be able to provide, on request, a certificate of analysis stating peptide identity and purity by HPLC and mass spectrometry, the lot number, the date of analysis, and the storage recommendation. Where a study used a modified peptide — R13A-MOTS-c, for example — the modification should be stated explicitly, because the wild-type and the analogue are not interchangeable in uptake assays [4]. Sequence should be stated in single-letter or three-letter form so that it can be checked against the published wild-type sequence [4].

Price and sourcing considerations

Price for a research peptide is driven by synthesis scale, purity grade and the cost of quality control rather than by any clinical claim, and the evidence block contains no pricing data. Buyers comparing listings should compare like with like: purity specification, quantity per vial, whether the certificate of analysis is lot-specific, and whether the sequence and any modification are declared. A listing that omits the sequence or the purity method cannot be evaluated against the studies cited above.

If you are reading this for personal health reasons

This material is sold for laboratory research only, and we do not provide dosing or medical guidance. Anyone considering a compound for themselves should speak to a licensed clinician.

Sources

• [1] https://europepmc.org/article/PMC/PMC13485304
• [2] https://europepmc.org/article/PMC/PMC13394035
• [3] https://europepmc.org/article/PMC/PMC13257931
• [4] https://europepmc.org/article/PMC/PMC13199819
• [5] https://europepmc.org/article/PMC/PMC13204372
• [6] https://europepmc.org/article/PMC/PMC13113351
• [7] https://europepmc.org/article/PMC/PMC13055642
• [8] https://clinicaltrials.gov/study/NCT07678073
• [9] https://pubmed.ncbi.nlm.nih.gov/42633878/
• [10] https://europepmc.org/article/PMC/PMC13536784
• [11] https://europepmc.org/article/PMC/PMC13466091
• [12] https://pubmed.ncbi.nlm.nih.gov/42228044/