For decades, mitochondrial DNA was usually described as a compact genome for oxidative-phosphorylation proteins, ribosomal RNA, and transfer RNA. In 2015, Changhan Lee’s team reported a short open reading frame inside the mitochondrial 12S rRNA region that encodes a 16-amino-acid signaling peptide.
This compound is supplied exclusively for in vitro and preclinical research. It is not intended for human consumption, therapeutic application, or diagnostic use.
Mitochondrial-Derived Peptide Context
MOTS-c (Mitochondrial Open reading frame of the Twelve S rRNA type-c) is encoded within the mitochondrial genome rather than the nuclear genome. It belongs to the mitochondrial-derived peptide (MDP) literature, a research area focused on short open reading frames that can produce biologically active signaling molecules.
Early MOTS-c work helped establish that mitochondrial-encoded peptides can participate in cell-signaling models beyond local organelle housekeeping. That made MOTS-c a useful research tool for studying how mitochondrial sequence, cellular stress state, and nuclear transcription programs can interact.
Pathway Findings in Published Models
AMPK-Associated Signaling
The original 2015 paper evaluated MOTS-c in controlled cellular and animal model systems and reported changes in glucose-handling markers, substrate-use markers, and AMPK-associated signaling. The research framed MOTS-c as a mitochondrial-encoded signal connected to cellular nutrient-sensing pathways.
In nutrient-challenge mouse models, investigators tracked pathway markers rather than consumer-facing outcome claims. The RUO-relevant takeaway is the signaling architecture: MOTS-c was studied as a tool for probing AMPK-linked cellular state changes.
Activity-Linked Release Models
Later work reported that circulating MOTS-c changed during controlled physical-activity protocols and that skeletal-muscle tissue was part of the observed release pattern. In a research setting, those findings are useful because they connect a mitochondrial-encoded peptide to activity-state sampling and tissue-communication models.
That literature should not be read as a use claim. It is better understood as a mechanistic question: whether mitochondrial peptide signaling is one component of how cells record and transmit changes in physiological state under defined experimental conditions.
One-Carbon Pathway and AICAR
This makes MOTS-c useful for research questions about pathway crosstalk: mitochondrial coding sequence, one-carbon biochemistry, AICAR accumulation, AMPK signaling, and nuclear transcriptional response.
Age-Cohort Model Observations
Several studies also examined MOTS-c across age-stratified samples and animal cohorts. Reported endpoints included circulating MOTS-c abundance, mitochondrial-DNA variants affecting the MOTS-c sequence, and model-system readouts tied to cellular stress response.
- Circulating MOTS-c was measured across younger and older sample groups.
- Animal studies tracked locomotor, substrate-use, and pathway-marker endpoints.
- Population genetics work examined mitochondrial-DNA variants, including m.1382A>C, in centenarian cohorts.
For RUO copy, the important point is the research design: MOTS-c appears in literature involving mitochondrial genetics, age-stratified sampling, and cellular stress-response models. Those are model-system contexts, not product-use claims.
Mito-Nuclear Localization
In 2018, Kim et al. reported that MOTS-c can localize to the nucleus under defined stress conditions and participate in transcriptional regulation. A mitochondrial-encoded peptide entering the nucleus gave researchers a direct model for communication between mitochondrial sequence output and nuclear gene-expression programs.
This mito-nuclear signaling pathway is one reason MOTS-c remains prominent in pathway-mapping studies. It gives researchers a compact peptide model for asking how mitochondrial status can be coupled to nuclear transcriptional response.
What Makes MOTS-c Distinct in Research Literature
- Origin: Encoded by mitochondrial DNA rather than nuclear DNA.
- Nuclear localization: Reported to participate in gene-expression models under defined stress conditions.
- Activity-state sampling: Appears in controlled studies that measure peptide abundance across defined activity states.
- Age-cohort literature: Appears in age-stratified and mitochondrial-variant research designs.
Product Specifications
- Sequence: MRWQEMGYIFYPRKLR (16 amino acids)
- Molecular Weight: 2,174.64 g/mol
- CAS Number: 1627580-64-6
- Physical Form: Sterile lyophilized white powder
- Purity: ≥99% (verified by HPLC)
Key References
- Lee C, et al. Cell Metab. 2015;21(3):443-454.
- Kim SJ, et al. Cell Metab. 2018;28(3):516-524.
- Reynolds JC, et al. Nat Commun. 2021;12:470.
Browse MOTS-c 10mg with verified COA from Janoshik Analytical. For related mitochondrial and pathway-marker materials, explore NAD+, Epithalon, and 5-Amino-1MQ.