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MOTS-c

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MOTS-c
Identifiers
  • (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
PubChem CID
Chemical and physical data
FormulaC101H152N28O22S2
Molar mass2174.62 g·mol−1
3D model (JSmol)
  • 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=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

[edit]

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

[edit]
  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.
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