MOTS-c

MOTS-c

Identifiers
IUPAC name (4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-oxopentanoyl]amino]-5-[[(2S)-1-[[2-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
CAS Number	1627580-64-6
PubChem CID	146675088
Chemical and physical data
Formula	C101H152N28O22S2
Molar mass	2174.62 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)N
InChI InChI=1S/C101H152N28O22S2/c1-7-57(4)83(96(148)126-76(50-58-19-9-8-10-20-58)92(144)127-78(52-60-30-34-63(131)35-31-60)97(149)129-46-18-27-79(129)95(147)122-69(25-16-44-112-100(107)108)86(138)118-67(23-13-14-42-102)87(139)124-74(49-56(2)3)91(143)123-73(98(150)151)26-17-45-113-101(109)110)128-94(146)75(51-59-28-32-62(130)33-29-59)116-81(133)55-115-85(137)72(41-48-153-6)121-90(142)71(37-39-82(134)135)119-89(141)70(36-38-80(104)132)120-93(145)77(53-61-54-114-66-22-12-11-21-64(61)66)125-88(140)68(24-15-43-111-99(105)106)117-84(136)65(103)40-47-152-5/h8-12,19-22,28-35,54,56-57,65,67-79,83,114,130-131H,7,13-18,23-27,36-53,55,102-103H2,1-6H3,(H2,104,132)(H,115,137)(H,116,133)(H,117,136)(H,118,138)(H,119,141)(H,120,145)(H,121,142)(H,122,147)(H,123,143)(H,124,139)(H,125,140)(H,126,148)(H,127,144)(H,128,146)(H,134,135)(H,150,151)(H4,105,106,111)(H4,107,108,112)(H4,109,110,113)/t57-,65-,67-,68-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,83-/m0/s1 Key:WYTHCOXVWRKRAH-LOKRTKBUSA-N

MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino-acid peptide that in humans is encoded by the mitochondrial MT-RNR1 gene, with the amino acid sequence MRWQEMGYIFYPRKLR. ^[1] It is believed to be involved in regulating metabolism of glucose by skeletal muscle tissue. It is upregulated in response to exercise, and is considered an exercise mimetic, as well as having other potential medical applications. ^{[2] [3] [4] [5] [6] [7] [8]}

MOTS-c binds to casein kinase 2. ^[9]

Society and culture

Researchers discovered MOTS-c in 2015. ^[10]

MOTS-c is not approved to treat any medical condition and is banned by the World Anti-Doping Agency, explicitly beginning in 2024. ^[11]

References

1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P (March 2015). "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance". Cell Metabolism. 21 (3): 443–454. doi:10.1016/j.cmet.2015.02.009. PMC   4350682 . PMID   25738459.
2. Lee C, Kim KH, Cohen P (November 2016). "MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism". Free Radical Biology & Medicine. 100: 182–187. doi:10.1016/j.freeradbiomed.2016.05.015. PMC   5116416 . PMID   27216708.
3. Dieli-Conwright, Christina M.; Sami, Nathalie; Norris, Mary K.; Wan, Junxiang; Kumagai, Hiroshi; Kim, Su-Jeong; Cohen, Pinchas (19 August 2021). "Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors". Scientific Reports. 11 (1): 16916. Bibcode:2021NatSR..1116916D. doi:10.1038/s41598-021-96419-z. ISSN   2045-2322. PMC   8376922 . PMID   34413391.
4. Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z (January 2023). "MOTS-c Functionally Prevents Metabolic Disorders". Metabolites. 13 (1): 125. doi: 10.3390/metabo13010125 . PMC   9866798 . PMID   36677050.
5. Kal S, Mahata S, Jati S, Mahata SK (February 2024). "Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives". Peptides. 172 171147. doi:10.1016/j.peptides.2023.171147. PMC   10838678 . PMID   38160808.
6. Thakur R, Chauhan A, Moudgil H, Singh S, Devi R (December 2025). "Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases". Molecular Neurobiology. 62 (12): 15871–15884. doi:10.1007/s12035-025-05198-5. PMID   40715951.
7. Tero-Vescan A, Degens H, Matsakas A, Ștefănescu R, Ősz BE, Slevin M (August 2025). "Exercise-Induced Muscle-Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging". Pharmaceuticals. 18 (8): 1222. doi: 10.3390/ph18081222 . PMC   12389176 . PMID   40872612.
8. Ran Y, Guo Z, Zhang L, Li H, Zhang X, Guan X, Cui X, Chen H, Cheng M (May 2025). "Mitochondria‑derived peptides: Promising microproteins in cardiovascular diseases (Review)". Molecular Medicine Reports. 31 (5): 1–17. doi:10.3892/mmr.2025.13492. PMC   11924172 . PMID   40084698.
9. Kumagai, Hiroshi; Kim, Su-Jeong; Miller, Brendan; Natsume, Toshiharu; Lee, Shin Hyung; Sato, Ayaka; Ramirez, Ricardo; Wan, Junxiang; Mehta, Hemal H; Yen, Kelvin; Cohen, Pinchas (May 2023). "Casein kinase 2 is a direct binding partner and a functional target of the exercise-mimetic microprotein MOTS-c". Physiology. 38 (S1) 5725846. doi:10.1152/physiol.2023.38.S1.5725846. ISSN   1548-9213. S2CID   258979715.
10. Wan, Wei; Zhang, Lieliang; Lin, Yue; Rao, Xiuqing; Wang, Xifeng; Hua, Fuzhou; Ying, Jun (2023). "Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging". Journal of Translational Medicine. 21 (1): 36. doi: 10.1186/s12967-023-03885-2 . PMC   9854231 . PMID   36670507.
11. "Explanation of Key Changes on the 2024 WADA Prohibited List". 13 October 2023. Retrieved 6 December 2023.