MOTS-C

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within mitochondrial DNA, one of a small group of mitochondrial-derived peptides. Preclinical research on the MOTS-c peptide has examined its inhibition of the folate cycle and resulting AMPK activation, insulin sensitivity in high-fat-fed and aging mice, physical capacity in old mice, muscle atrophy after limb immobilization, and direct binding to the protein kinase CK2. Research Market supplies MOTS-c with purity and identity data for each lot reported on its certificate of analysis. It is sold strictly for laboratory research use.

Chemical structure and identification

• Molecular formula: C₁₀₁H₁₅₂N₂₈O₂₂S₂
• Molecular weight: 2174.6 g/mol
• CAS number: 1627580-64-6
• PubChem CID: 146675088
• Amino acid sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR)
• Synonyms: Mitochondria-derived peptide MOTS-c
• Form: Lyophilized powder
• Analytical methods: RP-HPLC for purity and mass spectrometry for identity, reported on the batch certificate of analysis

Research applications

• Discovery and metabolic signaling: Identified as a peptide encoded by a short open reading frame in the mitochondrial 12S rRNA; its cellular actions inhibited the folate cycle and de novo purine biosynthesis, leading to AMPK activation, with skeletal muscle as its apparent primary target organ [1]
• Aging and physical capacity: MOTS-c treatment was reported to increase physical performance in young, middle-aged and old mice and to regulate nuclear genes related to metabolism and proteostasis; in humans, exercise induced endogenous MOTS-c expression [2]
• CK2 as a direct target: MOTS-c bound and activated the kinase CK2 in cell-free systems, and its effects on muscle glucose uptake and atrophy in mice were blunted when CK2 activity was suppressed; the natural K14Q variant bound CK2 poorly [3]
• Immobilization-induced atrophy: In mice with a cast-immobilized limb, MOTS-c treatment was associated with smaller muscle mass loss, normalized AKT and FOXO phosphorylation, lower circulating inflammatory cytokines and lower muscle fatty acid levels [4]

Reference citations

1. Lee C. et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 21(3):443–454. PMID 25738459 · DOI
2. Reynolds J.C. et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun, 12(1):470. PMID 33473109 · DOI
3. Kumagai H. et al. (2024). MOTS-c modulates skeletal muscle function by directly binding and activating CK2. iScience, 27(11):111212. PMID 39559755 · DOI
4. Kumagai H. et al. (2024). Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration. Am J Physiol Endocrinol Metab, 326(3):E207–E214. PMID 38170165 · DOI

Compound data from PubChem CID 146675088. Literature summaries describe published preclinical research and are not claims about this product’s effects in humans or animals.