# MOTS-c > Source: https://chooseunscripted.com/peptide/mots-c/ > Content type: Peptide research profile > Last updated: September 4, 2026 **For research use only. Not for human or veterinary use.** ## Multi-Compound Blend No ## Product URL ## Scientific / Common Name MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) ## Alternative Names / Synonyms MOTS-c; Mitochondrial-Derived Peptide MOTS-c; MDP MOTS-c; Mitochondrial Open Reading Frame of the 12S rRNA Type-c ## Molecular Formula C₁₀₁H₁₅₂N₂₈O₂₂S₂ ## Molecular Weight 2174.6 g/mol ## CAS Number 1627580-64-6 ## Clinical Development Phase Phase 2 ## Regulatory Status Investigational; not FDA approved. ## Peptide Classification Mitochondrial-Derived Peptide ## Primary Research Focus Mitochondrial signaling; cellular energy metabolism; AMPK activation; insulin sensitivity; glucose homeostasis; metabolic stress response; skeletal muscle signaling; healthy aging ## Mechanism Summary MOTS-c is a **16-amino-acid mitochondrial-derived peptide encoded within mitochondrial 12S rRNA**. Unlike many signaling peptides encoded by nuclear DNA, MOTS-c originates from mitochondrial genetic information and participates in communication between mitochondria and the rest of the cell. Research suggests that MOTS-c influences **cellular energy metabolism primarily through the folate-AICAR-AMPK pathway**. Activation of AMP-activated protein kinase (AMPK), a central cellular energy sensor, has been associated in preclinical studies with changes in glucose utilization, insulin sensitivity, fatty-acid metabolism, and adaptation to metabolic stress. Under cellular stress, MOTS-c has also been reported to **translocate to the nucleus**, where it may influence expression of genes involved in antioxidant responses and stress adaptation. These findings support the concept of MOTS-c as a mitochondrial-to-nuclear signaling molecule rather than a peptide acting through one clearly established cell-surface receptor. ## Evidence Summary Most of the published MOTS-c evidence has historically come from **cell and animal studies** examining metabolic regulation, insulin sensitivity, exercise physiology, inflammation, and age-related changes. These studies have repeatedly implicated AMPK signaling and skeletal muscle as important components of MOTS-c biology. A major development occurred in 2026 with the launch of **MOTS-MET, a randomized Phase 2a clinical trial** evaluating MOTS-c in adults with prediabetes and overweight or obesity. The study plans to enroll approximately 120 participants and is assessing insulin sensitivity, HbA1c, fasting glucose, glucose tolerance, metabolic markers, and safety. The trial is currently recruiting, and **no efficacy results have yet been posted**. As a result, claims involving metabolic improvement, insulin sensitivity, exercise capacity, longevity, or other proposed human effects remain investigational until controlled human results become available. ## Key References - Wan W, et al. [*Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging.*](https://pubmed.ncbi.nlm.nih.gov/36670507/?utm_source=chatgpt.com) **Journal of Translational Medicine.** 2023. - Lee C, et al. [*The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.*](https://pubmed.ncbi.nlm.nih.gov/25738459/) **Cell Metabolism.** 2015. - Kim KH, et al. [*The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress.*](https://pubmed.ncbi.nlm.nih.gov/29983246/) **Cell Metabolism.** 2018. - ClinicalTrials.gov. [*MOTS-c for Improving Insulin Sensitivity in Adults With Prediabetes and Overweight/Obesity, NCT07505745.*](https://clinicaltrials.gov/study/NCT07505745) **Phase 2a clinical trial.** ## Last Scientifically Reviewed September 4, 2026 ## Quick Definition MOTS-c is a 16-amino-acid mitochondrial-derived peptide studied for its role in cellular energy metabolism, AMPK signaling, insulin sensitivity, stress adaptation, and metabolic homeostasis. ## Targets / Receptors AMPK signaling; folate-AICAR metabolic pathway; mitochondrial-to-nuclear signaling; skeletal muscle metabolism; glucose utilization; insulin sensitivity; cellular stress-response pathways ## Safety & Limitations MOTS-c remains **investigational**, and its long-term safety profile in humans has not been established. Much of the current mechanistic and efficacy literature comes from cell and animal models, which cannot be assumed to predict equivalent outcomes in humans. The ongoing Phase 2a MOTS-MET trial includes structured monitoring of adverse events, laboratory findings, vital signs, ECG measurements, and potential immunogenicity. Because results have not yet been reported, the safety and efficacy of MOTS-c for metabolic disorders remain undetermined. Claims involving **longevity, weight reduction, enhanced exercise performance, or treatment of metabolic disease** should therefore be regarded as investigational rather than established clinical effects. ## Frequently Asked Questions - ### What is MOTS-c? MOTS-c is a 16-amino-acid peptide encoded by mitochondrial DNA. It is studied as a mitochondrial signaling molecule involved in energy metabolism, cellular stress responses, and metabolic regulation. - ### What does MOTS-c target? MOTS-c does not have one established primary cell-surface receptor. Research suggests that its effects involve AMPK signaling, the folate-AICAR pathway, skeletal muscle metabolism, and mitochondrial-to-nuclear communication. - ### What is MOTS-c being researched for? MOTS-c is being investigated in research involving insulin sensitivity, glucose metabolism, metabolic stress, skeletal muscle function, exercise physiology, inflammation, and healthy aging. - ### Has MOTS-c been studied in humans? Yes. A Phase 2a randomized clinical trial began in 2026 to evaluate MOTS-c in adults with prediabetes and overweight or obesity. The trial is currently recruiting and has not yet reported efficacy results. - ### Is MOTS-c FDA approved? No. MOTS-c is not FDA approved and remains investigational. ## Available Research Compound - [Product page](https://chooseunscripted.com/shop/mots-c/index.md)