MOTS-c: Mitochondrial Peptide in Metabolic Research

EXOMA Scientific Team · Publicado el 8 de mayo de 2026 · Actualizado el 18 de agosto de 2026

MOTS-c is a 16-amino-acid peptide encoded in the mitochondrial genome. Review of its mechanism, preclinical studies, and relevance for metabolic research.

Chemical identity

MOTS-c (Mitochondrial Open Reading frame of the 12S rRNA-c) is a peptide of 16 amino acids encoded within the mitochondrial genome -not nuclear-, which distinguishes it from practically all other endogenous peptides. It was described by Lee et al. in 2015 (USC Davis School of Gerontology).

Sequence: MRWQEMGYIFYPRKLR

Molecular mechanism

The preclinical literature describes multiple pathways:

1. AMPK activation (sensor energético celular)
2. Modulation of the folate-methionine pathway → biosíntesis de purinas
3. Regulation of glucose homeostasis vía mejora de la sensibilidad a insulina
4. Nuclear translocation under metabolic stress → modulation of response genes

Preclinical studies

Endogenous levels and aging

The plasma levels of MOTS-c decrease significantly with age and with insulin resistance, which has positioned the peptide as an object of study in gerontology and experimental metabolic medicine.

Reconstitution

Vial of 10 mg reconstituted with 2 mL of bacteriostatic water:

• Concentration: 5 mg/mL
• Volume for 5 mg: 1 mL

Frequency described in the literature

The preclinical studies describe daily or every-other-day administrations, with relatively short half-lives. The optimal frequency remains the object of active research.

Required purity

• HPLC ≥99%
• Sequence confirmation by mass spectrometry
• COA per batch

Key differentiation

Unlike secretagogue peptides such as Ipamorelin or CJC-1295 that act on the pituitary, MOTS-c acts directly at the mitochondrial level, which makes it a unique tool for investigating the mitochondria-metabolism axis.

References

1. Lee C, 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.2015.02.009. PMID 25738459. (animal/in vitro)
2. Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. doi:10.1038/s41467-020-20790-0. PMID 33473109. (animal/humano)
3. Kim KH, et al. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metab. 2018;28(3):516-524.e7. doi:10.1016/j.cmet.2018.06.008. PMID 29983246. (in vitro/animal)

Products available at EXOMA

• MOTS-c