MOTS-c 40mg

MOTS-c 40mg — Mitochondria-Derived Peptide for Metabolic and Mitochondrial Research

MOTS-c 40mg is a research-grade lyophilised preparation of MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c), a 16-amino-acid peptide encoded within the mitochondrial genome — specifically within the 12S ribosomal RNA gene. First characterised by Lee et al. in 2015, MOTS-c represents a novel class of mitochondria-derived peptides (MDPs) that translocate from mitochondria to the nucleus in response to metabolic stress and are associated with AMPK (AMP-activated protein kinase) signalling activation. Each vial supplied by AbsoluteBioLab contains 40mg of MOTS-c, verified by reverse-phase high-performance liquid chromatography (RP-HPLC) to a minimum purity of ≥99.0%, with identity confirmed by electrospray ionisation mass spectrometry (ESI-MS).^[1]

The sequence of MOTS-c is MRWQEMGYIFYPRKLR-NH₂ (16 amino acids, C-terminal amide), with a molecular weight of 2,174.6 Da (free base). MOTS-c is translated from a non-canonical open reading frame within the mitochondrial 12S rRNA gene using a modified genetic code, making it one of only a small number of peptides known to be encoded by the mitochondrial genome. Published research has examined its relationship with folate/purine metabolism, AMPK-associated signalling, mitochondrial-to-nuclear communication, and stress-responsive gene expression in cell and animal models. These findings are primarily preclinical and do not establish clinical efficacy, safety, or approved therapeutic use in humans.

Compound Identity

Analytical Specification and Release Testing

Every batch of MOTS-c 40mg supplied by AbsoluteBioLab is subjected to a two-tier analytical release protocol. Purity is determined by RP-HPLC (C18 column, UV 220 nm) confirming ≥99.0% purity. Molecular identity is confirmed by ESI-MS with the observed [M+nH]ⁿ⁺ ion series matched against the theoretical mass of MOTS-c (MW 2,174.6 Da). Batch-specific results are documented in the Certificate of Analysis.

Mechanism of Action — Mitochondrial Retrograde Signalling and AMPK-Associated Pathway Activation

MOTS-c is a mitochondria-derived peptide (MDP) that has been reported to function as a retrograde signalling molecule, communicating mitochondrial metabolic status to the nucleus and coordinating metabolic responses in preclinical models. Under conditions of metabolic stress — including glucose restriction and oxidative stress — MOTS-c has been reported to translocate from the mitochondrial matrix to the cytoplasm and nucleus, where it is associated with AMPK (AMP-activated protein kinase) pathway activation through a mechanism involving the folate cycle and AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) production.^[1]

The proposed mechanism involves MOTS-c inhibition of the folate cycle enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase 2), which leads to accumulation of AICAR — a natural AMPK activator. AICAR activates AMPK by allosteric binding to the γ subunit, mimicking elevated AMP:ATP ratios. AMPK activation is associated with phosphorylation of downstream metabolic regulators including ACC (acetyl-CoA carboxylase), PGC-1α (promoting mitochondrial biogenesis), and SIRT1. These downstream associations — SIRT1, NRF2, FoxO1, and mTOR — have been reported in preclinical models and represent pathway associations rather than validated direct molecular binding targets of MOTS-c.^{[1] [2]}

It should be noted that the mechanistic understanding of MOTS-c signalling continues to evolve. The 2015 Lee et al. work linked MOTS-c to folate/purine metabolism and AMPK activation; subsequent research has explored additional signalling contexts. Researchers should consult the primary literature for the current state of mechanistic evidence.

Research Applications

Metabolic Stress and AMPK Signalling Research

MOTS-c has been studied in the context of metabolic stress responses and AMPK-associated signalling in cell culture models. In skeletal muscle cell culture models (C2C12, L6), MOTS-c treatment has been associated with AMPK activation and changes in glucose metabolism markers. In high-fat diet mouse models, MOTS-c administration has been reported to affect glucose tolerance and insulin sensitivity — findings that are preclinical and do not establish clinical efficacy in humans.^[1]

Mitochondrial-to-Nuclear Communication Research

MOTS-c is used as a tool compound in research investigating mitochondrial retrograde signalling — the communication of mitochondrial metabolic status to the nuclear genome. Research using MOTS-c in cell models has contributed to understanding how mitochondria-derived signals coordinate nuclear gene expression in response to metabolic stress, including the role of the folate cycle and AICAR in this signalling pathway.^[1]

Cellular Senescence and Metabolic Research

MOTS-c has been used in preclinical research examining the relationship between mitochondrial signalling, AMPK activity, and metabolic gene expression in cell culture models of metabolic stress and cellular senescence. Published pre-clinical findings support its use as a research tool in metabolic biology programmes investigating mitochondrial-derived peptide signalling. These findings are from cell and animal models and do not establish clinical outcomes in humans.^[2]

Exercise Biology and Skeletal Muscle Research

MOTS-c has been studied in the context of exercise biology and skeletal muscle metabolism. Some research has reported changes in circulating MOTS-c levels in association with physical activity; however, the precise cellular source of circulating MOTS-c during exercise remains an area of active investigation, and the characterisation of MOTS-c as a myokine released specifically from skeletal muscle during exercise has not been definitively established. Researchers should consult the current primary literature for the evolving understanding of MOTS-c’s role in exercise biology.^[2]

Inflammation and Immune Regulation Research

MOTS-c has been studied in macrophage models for its effects on inflammatory signalling. Research has reported associations between MOTS-c and NRF2 pathway activation and changes in cytokine production (TNF-α, IL-6, IL-1β) in LPS-stimulated macrophage models. These findings are from cell-based models and do not establish clinical anti-inflammatory efficacy.^[2]

Storage and Transport

Note: Reconstituted solution storage, solvent selection, working concentration, and stability period guidance are not provided, consistent with AbsoluteBioLab’s Research Use Only supply policy. Researchers should refer to their institutional SOPs and the published literature for handling reconstituted peptide solutions.

Batch Documentation

Every batch of MOTS-c 40mg dispatched by AbsoluteBioLab is accompanied by a batch-specific Certificate of Analysis confirming RP-HPLC purity (≥99.0%), ESI-MS identity, endotoxin result, and Karl Fischer moisture. CoA documents are available via the Certificate of Analysis Portal. For further information on our analytical methodology, refer to the guide on HPLC Purity in Peptide Research.

Frequently Asked Questions

Related Research Guides

References

1. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.017
2. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12:470. doi:10.1038/s41467-020-20790-0
3. Kim KH, Son JM, Benayoun BA, Lee C. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metab. 2018;28(4):516–524. doi:10.1016/j.cmet.2018.06.008
4. Bhullar KS, Hubbard BP. Lifespan and healthspan extension by resveratrol. Biochim Biophys Acta Mol Basis Dis. 2015;1852(6):1209–1218. doi:10.1016/j.bbadis.2015.01.012 — Context: AMPK/SIRT1 signalling axis background.