MOTS-c — wholesale 10-vial kits

Research context

MOTS-c — mitochondrial open reading frame of the 12S rRNA type-c — is a 16-residue peptide encoded by a short open reading frame inside the mitochondrial 12S rRNA gene, not in the nuclear genome (UniProt A0A0C5B5G6). It was described in Cell Metabolism in 2015 and belongs to the small group of mitochondrial-derived peptides that also includes humanin and the SHLPs. Its discovery supported the idea that mitochondria signal to the rest of the cell with peptides, not only with metabolites and reactive species.

The sequence is short, unmodified and distinctly hydrophobic for its length, with two methionines, a tryptophan and a C-terminal basic cluster (Arg-Lys-Leu-Arg). That cluster is the part most often implicated in nuclear import, and the two methionines are the main analytical liability, since sulfoxide formation adds +16 Da per residue. Because the peptide is encoded in mitochondrial DNA, it is also read differently from nuclear transcripts — a point that matters when designing expression constructs or interpreting sequence-based searches.

Mechanistically the best-described route is metabolic rather than receptor-mediated. The 2015 work reported that MOTS-c inhibits the folate–methionine pathway and de novo purine biosynthesis, raising AICAR and activating AMP-activated protein kinase, with downstream effects on glucose handling in skeletal-muscle and cell models. A 2018 study in Cell Metabolism showed that under metabolic stress the peptide translocates to the nucleus and associates with antioxidant-response-element regions, influencing stress-response gene expression — the mitochondrial–nuclear communication arm of the literature. A 2021 report in Nature Communications characterized it as an exercise-responsive, mitochondrially encoded regulator of age-dependent physical decline and muscle homeostasis in mice.

As a research tool MOTS-c is used as a stimulus in AMPK phosphorylation and metabolic-flux assays (Seahorse respirometry, glucose-uptake panels in myotubes and adipocytes), in nuclear-translocation and ChIP experiments with labelled or tagged analogs, in rodent exercise and metabolic physiology models, and as an analytical reference standard when circulating MOTS-c is measured by LC-MS or immunoassay in biomarker studies. Human work indexed to date is largely observational biomarker measurement rather than interventional.

Regulatory position, stated factually: MOTS-c is not FDA-approved and is not the active ingredient of any approved product. FDA lists MOTS-c among bulk drug substances whose compounding nominations were withdrawn by the nominators; MOTS-c-related bulk substances were discussed at the Pharmacy Compounding Advisory Committee meeting of July 23–24, 2026, and the HHS interim enforcement-discretion notice published in the Federal Register on October 30, 2026 addresses certain peptide bulk substances in 503A compounding pending rulemaking. That notice is not an approval and is directed at licensed compounders. WholesalePeptide.us supplies MOTS-c as a research reference standard for in-vitro, analytical and preclinical laboratory research.

The sequence contains two methionines, so oxidized species (+16 and +32 Da) are the most common impurities to look for. The lot COA reports both RP-HPLC purity and the LC-MS mass.

Research areas

• mitochondrial-derived peptide signaling
• AMPK activation and the folate–purine pathway
• skeletal-muscle metabolism in rodent models
• mitochondrial–nuclear communication
• exercise physiology biomarkers
• AMPK phosphorylation and respirometry assays
• mitochondrial-derived peptide biomarker quantitation

U.S. regulatory status of the compound (as an active ingredient): Not approved by the FDA. The material sold here is a research reference chemical, not a drug product.

Handling and storage

• Store lyophilized vials at −20 °C, sealed, protected from light and moisture.
• Let the vial equilibrate to room temperature before opening to limit condensation.
• Reconstitute in an appropriate sterile buffer or solvent according to your laboratory SOP.
• Contains two methionines; minimize air exposure, aliquot promptly and avoid repeated freeze–thaw.