MOTS-C — Research Summary
Overview
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-C) is a 16-amino acid peptide encoded by the mitochondrial genome. Discovered in 2015, it represents a novel class of mitochondrial-derived peptides with implications for metabolic research. MOTS-c was first described by Dr. Changhan Lee and colleagues at the University of Southern California in 2015, marking a significant milestone in the understanding of the mitochondrial genome's coding potential. Prior to this discovery, the mitochondrial genome was thought to encode only 13 proteins, 22 transfer RNAs, and 2 ribosomal RNAs. The identification of MOTS-c as a biologically active peptide encoded within the 12S rRNA gene revealed a previously unrecognized layer of mitochondrial-nuclear communication. Subsequent research has documented that MOTS-c is an exercise-responsive peptide, with endogenous levels increasing measurably in skeletal muscle and circulation following physical activity. The peptide's documented interactions with the Folate-AICAR-AMPK pathway and its ability to translocate to the nucleus during metabolic stress have established it as a subject of significant interest in aging, exercise physiology, and metabolic research.
Compound Profile
The following specifications characterize the MOTS-C research compound as supplied for laboratory investigation purposes.
| Compound Name | MOTS-C |
| Designation | MOTS-C — 10 mg |
| Sequence / Structure | MRWQEMGYIFYPRKLR (16 amino acids) |
| Purity | ≥99% |
| Form | Lyophilized powder |
| Vial Size | 10mg |
| Storage | Refrigerated after reconstitution |
| Research Category | Mitochondrial Research |
| Series | Metabolic Series |
| SKU | MS-10 |
Published Research
The following findings have been documented in peer-reviewed publications and scientific literature. These summaries reflect reported observations and are presented for informational purposes in support of laboratory research activities.
- A landmark study published in Nature Communications (Reynolds et al., 2021) demonstrated that MOTS-c is an exercise-induced peptide that significantly enhanced physical performance in young, middle-aged, and old mice, with late-life treatment increasing physical capacity and healthspan markers.
- Research in Cell Metabolism (Lee et al., 2015) showed that MOTS-c targets skeletal muscle and enhances glucose metabolism, with implications for obesity, diabetes, and longevity research.
- Studies documented in Diabetes & Metabolism Journal showed that plasma MOTS-c levels decline with age in humans, and that exercise considerably raises endogenous MOTS-c levels in skeletal muscle and circulation.
- A 2023 review in Frontiers in Physiology documented MOTS-c's role in regulating stress adaptation, energy metabolism, insulin sensitivity, and aging-related physiological processes through the Folate-AICAR-AMPK pathway.
These findings reflect outcomes observed in controlled research settings and published study protocols. Individual experimental conditions, model organisms, and methodologies varied across studies. Results observed in preclinical and clinical research settings may not be generalizable.
Mechanism of Action
MOTS-c is proposed to act through the Folate-AICAR-AMPK pathway, translocating to the nucleus during metabolic stress to regulate expression of genes with antioxidant response elements.
The mechanisms described above have been characterized through published research methodologies including receptor binding assays, gene expression analyses, cell culture experiments, and in vivo preclinical models. Mechanistic understanding continues to evolve as additional research is published.
Research Context
Mitochondrial-derived peptide research represents a relatively new and rapidly evolving field in molecular biology. Since the discovery that the mitochondrial genome encodes bioactive peptides beyond the traditionally recognized 13 proteins, researchers have identified several mitochondrial-derived peptides (MDPs) with potential significance for understanding cellular energy metabolism, stress adaptation, and aging-related processes. This class of peptides has been documented to interact with metabolic pathways including AMPK signaling, folate metabolism, and antioxidant response element regulation. Research has examined how endogenous levels of these peptides change with age and physical activity, providing insights into their potential roles in metabolic homeostasis. Studies have employed exercise physiology models, aging cohorts, and metabolic stress paradigms to characterize the biological significance of mitochondrial-derived peptides in both preclinical and clinical settings.
MOTS-C has been studied within this broader research context. The compound is classified under the Mitochondrial Research category and is part of the Metabolic Series in the Hot Peps research catalog. Researchers investigating mitochondrial research may find the published findings summarized above relevant to their experimental design and literature review processes.
Key Citations
The following references represent a selection of published studies relevant to MOTS-C research. Full-text articles may be accessed through their respective journal publishers or indexed databases such as PubMed.
- Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline. Nat Commun. 2021;12:470.PMID: 33473105
- Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis. Cell Metab. 2015;21(3):443-454.PMID: 25738459
- Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging.PMID: PMC9854231
This compound is part of the Metabolic Stack — appetite + metabolic signaling focus.
View Kit →Important Notice
MOTS-C is sold exclusively for in vitro research, laboratory use, and scientific investigation purposes. This compound is not intended for human consumption, veterinary use, or any therapeutic application. It is not intended to diagnose, treat, cure, or prevent any disease or medical condition.
All research findings, statistics, and outcomes referenced on this page have been sourced from published peer-reviewed studies and scientific literature. These summaries are provided for informational purposes to support qualified researchers in their laboratory investigations. Results documented in published research were obtained under specific experimental conditions and may not be reproducible in all settings.
Researchers are responsible for ensuring that their use of research compounds complies with all applicable local, state, and federal regulations governing laboratory research materials.
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All findings referenced on this page reflect outcomes reported in published research studies. This product is sold strictly for in vitro research, laboratory use, and scientific investigation only. Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.