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Peptency Academy · Compound

MOTS-c (mitochondrial open reading frame of the 12S rRNA-c)

MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16 amino acid peptide encoded by a short open reading frame inside the mitochondrial 12S rRNA gene, reported in 2015. Source sentenceHere we report a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c (mitochondrial open reading frame of the 12S rRNA-c)1 Cell Metab 2015 PubChem records it as Mots-c (CID 146675088): formula C101H152N28O22S2, about 2174.6 Da, CAS 1627580-64-6. Source sentenceTitle: Mots-c; MolecularFormula: C101H152N28O22S2; MolecularWeight: 2174.6; Synonyms include: 1627580-64-62 PubChem CID 146675088 It belongs to the mitochondrial-derived peptides, peptides encoded by short open reading frames in mitochondrial DNA, a group that also includes humanin. Source sentenceMitochondrial-derived peptides (MDP) are encoded by functional short open reading frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently discovered mitochondrial open reading frame of the 12S rRNA-c (MOTS-c).3 Aging Cell 2015 A 2026 review of approved and unapproved peptides that includes MOTS-c states that rigorous human safety data for the unapproved peptides are scarce. Source sentenceincluding [...] MOTS-C (mitochondrial ORF of the 12S rRNA type-c) [...] Many unapproved peptides [...] but rigorous human safety data are scarce4 Sports Med 2026

Version 1Edited Evidence through 38 sources

Regulatory content shown for: United States and the Americas.

Mitochondrial peptide, 16 residues

  • Catalog recordMOTS-c16 residuesabout 2174.6 DaSource sentenceTitle: Mots-c; MolecularFormula: C101H152N28O22S2; MolecularWeight: 2174.6; Synonyms include: 1627580-64-62 PubChem CID 146675088

Known, not known, contested

Known

  • MOTS-c is the 16 residue peptide MRWQEMGYIFYPRKLR: C101H152N28O22S2, about 2174.6 Da, monoisotopic mass 2173.1077 Da (PubChem CID 146675088). Source sentenceMolecularFormula: C101H152N28O22S2; MolecularWeight: 2174.6; MonoisotopicMass: 2173.1077409; Synonyms include: H-MRWQEMGYIFYPRKLR-OH2 PubChem CID 146675088
  • In cultured cells, a 2018 study traced MOTS-c into the nucleus after metabolic stress and measured nuclear gene expression and its interaction with the transcription factor NRF2. Source sentenceMOTS-c, a peptide encoded in the mitochondrial genome, translocates to the nucleus [...] following metabolic stress [...] interacted with ARE-regulating stress-responsive transcription factors, such as nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2)5 Cell Metab 2018
  • A PubMed search on 25 Oct 2026 found 266 records naming MOTS-c or MOTSc in the title or abstract, 59 of them reviews. Source sentence("MOTS-c"[tiab] OR "MOTSc"[tiab]): count 266; AND review[pt]: count 596 PubMed search for MOTS-c, 25 October 2026
  • Published primary studies cover analytical chemistry, cell cultures, mouse and rat models, and human studies that measured the body's own MOTS-c in blood or muscle. Source sentence266 records screened by title on 25 Oct 2026; examples: 30394592 (analytical), 29983246 (cells), 42611943 (mouse), 40403491 (rat), 34351816 and 36490309 (human, circulating MOTS-c measured)6 PubMed search for MOTS-c, 25 October 20267 Rapid Commun Mass Spectrom 20195 Cell Metab 20188 Elife 20269 Redox Biol 202510 J Appl Physiol (1985) 202111 Aging (Albany NY) 2022
  • ClinicalTrials.gov listed 9 records for MOTS-c on 25 Oct 2026, none with posted results; one of them gives MOTS-c to participants (NCT07505745). Source sentencequery.term MOTS-c: totalCount 9; hasResults false for all nine; NCT07505745 interventions: MOTS-c (MDP), Placebo12 ClinicalTrials.gov search, 25 October 202613 NCT07505745

Not known

  • No published study that gave MOTS-c to people was found in PubMed on 25 Oct 2026. The 5 MOTS-c records tagged as clinical trials measured MOTS-c already present in participants' blood or muscle, in exercise, heat, metformin and cardiology studies. Source sentenceAND clinical trial[pt]: 5 records (40674654 heat exposure, circulating and muscle MOTS-c; 36490309 metformin, circulating MOTS-c; 34413391 exercise, plasma MOTS-c; 34351816 exercise, plasma and muscle MOTS-c; 32052315 platelet reactivity cohort, MOTS-c blood levels)6 PubMed search for MOTS-c, 25 October 202610 J Appl Physiol (1985) 202111 Aging (Albany NY) 202214 Med Sci Sports Exerc 2025
  • The one registered trial that gives MOTS-c (NCT07505745, phase 2, China) was recruiting on 25 Oct 2026 with no posted results; its estimated primary completion date is 14 Feb 2027. Source sentenceoverallStatus RECRUITING; phases PHASE2; primaryCompletionDate 2027-02-14 (ESTIMATED); location country China; hasResults false13 NCT07505745
  • No human pharmacokinetic study of MOTS-c was found among the 266 PubMed records on 25 Oct 2026. Source sentencetitle screen of the 266 records on 25 Oct 2026: no record of MOTS-c given to humans; AND clinical trial[pt]: 5 records, all measuring endogenous MOTS-c6 PubMed search for MOTS-c, 25 October 2026

Contested

  • Measured levels in human blood depend on the method: a 2019 doping control study did not confirm by LC/MS the ELISA levels of 45.9 to 218.5 ng/mL found in 20 healthy people, and reported considerable differences between the two methods. Source sentenceendogenous levels of a reference population of 20 healthy subjects studied by ELISA experiments (45.9-218.5 ng/mL) could not be confirmed by LC/MS [...] considerable differences in measured MOTS-c levels were observed7 Rapid Commun Mass Spectrom 2019
  • Human studies on this page that report circulating MOTS-c used ELISA: a commercial competitive ELISA in the 2022 metformin study and an in-house ELISA in a 2026 exercise study, while the 2019 LC/MS study did not confirm ELISA reference levels. Source sentencePMID 36490309: "as measured using the commercially available competitive ELISA CEX132Hu"; PMID 42349896: "plasma MDP concentrations were measured using in-house enzyme-linked immunosorbent assay"; PMID 30394592: "endogenous levels of a reference population of 20 healthy subjects studied by ELISA experiments (45.9-218.5 ng/mL) could not be confirmed by LC/MS"11 Aging (Albany NY) 202215 Exp Physiol 20267 Rapid Commun Mass Spectrom 2019

Chemistry: MOTS-c as PubChem CID 146675088 records it

Sequence
MRWQEMGYIFYPRKLR
Length
16 residues
Formula
C101H152N28O22S2
Monoisotopic mass
2173.1077 Da
Average mass
2174.6 Da
CAS
1627580-64-6
PubChem CID
146675088
InChIKey
WYTHCOXVWRKRAH-LOKRTKBUSA-N
Synonyms
mitochondrial open reading frame of the 12S rRNA-c, Mitochondria-derived peptide MOTS-c, MOTS c, MOTSc, MOTs-C, H-MRWQEMGYIFYPRKLR-OH
Salt form
trifluoroacetate
Checked 25 October 2026 2 PubChem CID 146675088

Chemistry: identifiers and salt names

  • PubChem gives the InChIKey WYTHCOXVWRKRAH-LOKRTKBUSA-N and the systematic name L-methionyl-L-arginyl-L-tryptophyl-L-glutaminyl-L-alpha-glutamyl-L-methionylglycyl-L-tyrosyl-L-isoleucyl-L-phenylalanyl-L-tyrosyl-L-prolyl-L-arginyl-L-lysyl-L-leucyl-L-arginine. Source sentenceInChIKey: WYTHCOXVWRKRAH-LOKRTKBUSA-N; Synonyms include: L-Methionyl-L-arginyl-L-tryptophyl-L-glutaminyl-L-alpha-glutamyl-L-methionylglycyl-L-tyrosyl-L-isoleucyl-L-phenylalanyl-L-tyrosyl-L-prolyl-L-arginyl-L-lysyl-L-leucyl-L-arginine2 PubChem CID 146675088
  • PubChem lists a trifluoroacetate salt name, "MOTS-c (human) (trifluoroacetate salt)", under the same record. The masses on this page are for the peptide without a counterion. Source sentenceSynonyms include: MOTS-c (human) (trifluoroacetate salt)2 PubChem CID 146675088

Sequence

MRWQEMGYIFYPRKLR

Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg, the 16 residues of MOTS-c as PubChem CID 146675088 records them.
  • PubChem also writes the sequence as H-MRWQEMGYIFYPRKLR-OH, a one letter form in which H- and -OH mark the free amino and carboxyl ends; no modification is recorded. Source sentenceSynonyms include: H-MRWQEMGYIFYPRKLR-OH; Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg2 PubChem CID 146675088
  • Position 14 is lysine (K). The mitochondrial DNA variant m.1382A>C changes it to glutamine, giving the K14Q form of MOTS-c. Source sentencean Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c17 Aging (Albany NY) 2021

Which molecule does a MOTS-c certificate describe?

  • Read the sequence, formula and mass on the certificate of analysis. MRWQEMGYIFYPRKLR with C101H152N28O22S2 (average 2174.6 Da, monoisotopic 2173.1077 Da) is MOTS-c without a counterion as PubChem writes it. A label that says only "mitochondrial peptide" does not name one molecule. Source sentenceMolecularFormula: C101H152N28O22S2; MolecularWeight: 2174.6; MonoisotopicMass: 2173.1077409; Synonyms include: H-MRWQEMGYIFYPRKLR-OH2 PubChem CID 1466750883 Aging Cell 2015
  • K14Q MOTS-c is a different sequence: glutamine replaces lysine at position 14. A 2024 cell-free study measured binding of K14Q MOTS-c to the kinase CK2. Source sentencea naturally occurring MOTS-c variant, K14Q MOTS-c, has [...] binding to CK218 iScience 202417 Aging (Albany NY) 2021
  • Engineered analogues are different molecules: R13A-MOTS-c replaces arginine 13 with alanine (2026), and MP joins the cell-penetrating peptide (PRR)5 to MOTS-c (2021). Source sentencePMID 42142418: "we engineered R13A-MOTS-c by substituting the polar arginine at position 13 with alanine"; PMID 33861582: "(PRR)5, a cell penetrating peptides, as a carrier for MOTS-c" and "MP (cell-penetrating MOTS-c analogue)"19 Redox Biol 202620 ACS Chem Neurosci 2021
  • Humanin is a different mitochondrial-derived peptide; the 2015 discovery paper describes it as an earlier mtDNA-encoded signalling peptide. Source sentenceThe identification of a short open reading frame (sORF) in the mitochondrial DNA (mtDNA) that encodes a signaling peptide, humanin, suggests the possible existence of additional sORFs in the mtDNA.1 Cell Metab 2015
  • A 2019 LC/MS doping control method for MOTS-c in human plasma also covers animal MOTS-c analogues, four metabolites and two oxidation products. Source sentenceanimal MOTS-c analogues and four metabolites as well as two oxidation products were implemented7 Rapid Commun Mass Spectrom 2019

What is MOTS-c?

MOTS-c is a 16 amino acid peptide encoded inside the mitochondrial 12S rRNA gene, one of the mitochondrial-derived peptides. PubChem records it under CID 146675088 (C101H152N28O22S2, about 2174.6 Da, CAS 1627580-64-6), and its full name is mitochondrial open reading frame of the 12S rRNA-c. Source sentencea sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c (mitochondrial open reading frame of the 12S rRNA-c)1 Cell Metab 20152 PubChem CID 1466750883 Aging Cell 2015

Is MOTS-c a mitochondrial-derived peptide?

Yes. Mitochondrial-derived peptides are encoded by short open reading frames in mitochondrial DNA, and MOTS-c is the one encoded in the 12S rRNA region; humanin is another member of the group. Source sentenceMitochondrial-derived peptides (MDP) are encoded by functional short open reading frames in the mitochondrial DNA (mtDNA). These include humanin, and the recently discovered mitochondrial open reading frame of the 12S rRNA-c (MOTS-c).3 Aging Cell 20151 Cell Metab 2015

What is the molecular weight of MOTS-c?

PubChem gives an average molecular weight of 2174.6 Da and a monoisotopic mass of 2173.1077 Da for MOTS-c, C101H152N28O22S2 (CID 146675088), without a counterion. Source sentenceMolecularWeight: 2174.6; MonoisotopicMass: 2173.1077409; MolecularFormula: C101H152N28O22S22 PubChem CID 146675088

What has research studied about MOTS-c?

Published work covers where MOTS-c is encoded and its movement into the nucleus, binding to the kinase CK2 in cell-free systems, bacterial membrane and immune cell measurements, and mouse and rat models of exercise capacity, infection, lung injury and autoimmune islet damage. Human studies measured the body's own MOTS-c in blood or muscle; no published study that gave MOTS-c to people was found on 25 Oct 2026. Source sentence266 records screened by title on 25 Oct 2026; examples: 29983246 (nucleus), 39559755 (CK2), 42611943 (bacteria, monocytes, mouse peritonitis), 33473109 (mouse physical capacity), 29096170 (mouse MRSA), 40403491 (rat lung), 34320351 (mouse autoimmune diabetes); AND clinical trial[pt]: 5, all measuring endogenous MOTS-c6 PubMed search for MOTS-c, 25 October 20265 Cell Metab 201818 iScience 20248 Elife 202621 Nat Commun 202122 Mol Immunol 20179 Redox Biol 202523 Cell Rep 2021

Are there clinical trials of MOTS-c?

ClinicalTrials.gov listed 9 records for MOTS-c on 25 Oct 2026, none with posted results. One gives MOTS-c: a phase 2a randomised, double blind, placebo controlled trial in adults with prediabetes (NCT07505745, Hudson Biotech, China), recruiting, with an OGTT-derived insulin sensitivity measure (Matsuda index) as primary outcome. Five other records measure MOTS-c levels as an outcome or marker. Source sentencetotalCount 9; NCT07505745 officialTitle: "A Phase 2a, Randomized, Double-blind, Placebo-controlled Study [...] of MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes [...]"; RECRUITING; primary outcome: Change from baseline in OGTT-derived insulin sensitivity (Matsuda Index); site Shenzhen, China12 ClinicalTrials.gov search, 25 October 202613 NCT07505745

Is MOTS-c an FDA approved drug?

US

No. No FDA approved drug containing MOTS-c was found in openFDA Drugs@FDA on 25 Oct 2026. FDA's Category 2 compounding page lists MOTs-C under bulk drug substances nominated but withdrawn, and a Federal Register notice set a Pharmacy Compounding Advisory Committee discussion of MOTs-C-related bulk drug substances for 23 Jul 2026; neither is an approval. Source sentenceNOT_FOUND: No matches found! (products.active_ingredients.name MOTS-C; openfda.substance_name MOTS-C)24 openFDA Drugs@FDA query for MOTS-c, 25 October 202625 FDA, bulk drug substances Category 2 page, content current as of 22 April 202626 Federal Register 2026-07361, 16 April 2026

Is MOTS-c on the WADA Prohibited List?

International

Yes. The WADA 2026 Prohibited List names MOTS-c in class S4.4.1, among activators of the AMP-activated protein kinase (AMPK), within S4 Hormone and metabolic modulators, prohibited at all times. Source sentenceS4 HORMONE AND METABOLIC MODULATORS PROHIBITED AT ALL TIMES (IN- AND OUT-OF-COMPETITION) ... S4.4. METABOLIC MODULATORS S4.4.1 Activators of the AMP-activated protein kinase (AMPK), e.g. ... AICAR, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)27 WADA Prohibited List 2026

Evidence map: MOTS-c by model level

Primary studies of MOTS-c (MRWQEMGYIFYPRKLR), by model and by what was measured. Reviews are not counted. An empty cell means: not mapped yet.
ModelChemistry and analyticalPharmacokineticsReceptor binding and signallingTissue histologyBiomarkersClinical endpoint
Analytical only (no biological model)Chemistry and analytical1Not mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yet
In vitro or ex vivoNot mapped yetNot mapped yetReceptor binding and signalling7Not mapped yetNot mapped yetNot mapped yet
RodentNot mapped yetNot mapped yetReceptor binding and signalling5Tissue histology5Biomarkers6Not mapped yet
Other animalNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yet
Human, uncontrolledNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yet
Human, randomisedNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yet

12 studies countedEvidence level facet: L2. A design scale, not a measure of strength or quality.

Counts only the exact match primary studies reviewed for this page on 25 October 2026, out of 266 PubMed records found for MOTS-c or MOTSc. Studies that measured the body's own MOTS-c without giving it, and an engineered analogue, are in the study list and are not counted; reviews are never counted. Empty cells are not mapped yet.

Reading the evidence map

  • The Academy level is a design scale, not a measure of how well a molecule works: L0 chemistry or analytical work, L1 cells or tissue, L2 animals, L3 uncontrolled human reports, L4 randomised human trials. Source sentencePolicy, evidence levels; Policy, level table31 Peptency Academy sourcing policy, version 1
  • Counted from the study table on this page: 12 primary studies that gave or tested MOTS-c itself are chemistry, cell or animal work (L0 to L2). The 6 other studies measured the body's own MOTS-c or tested an analogue and are not counted. No study that gave MOTS-c to people was found, so the highest level reached is L2. Source sentencestudy table on this page: 1 analytical, 11 with cell and animal work counted as exact; 6 related form (5 endogenous MOTS-c measurements, 1 analogue); AND clinical trial[pt]: 5, all measuring endogenous MOTS-c6 PubMed search for MOTS-c, 25 October 2026

Who produced this evidence

  • Seven of the 12 counted studies list authors at the University of Southern California's Leonard Davis School of Gerontology, where the 2015 discovery paper was written by Changhan Lee, Pinchas Cohen and colleagues. Source sentenceAffiliations: Leonard Davis School of Gerontology, University of Southern California, Los Angeles (25738459, 29983246, 33473109, 39559755, 42611943, 33468709, 34320351); USC Leonard Davis School of Gerontology, Los Angeles (42324588); authors Lee C ... Cohen P (25738459)1 Cell Metab 20155 Cell Metab 201821 Nat Commun 202118 iScience 20248 Elife 202617 Aging (Albany NY) 202123 Cell Rep 202129 Inflamm Regen 2026
  • Competing interest statements in papers from that group state that Changhan Lee or Pinchas Cohen is a consultant and shareholder of CohBar, Inc., and a 2024 paper states that UCLA licensed the intellectual property on MOTS-c, with Cohen listed as an inventor, to CohBar. Source sentencePMID 39559755: "Pinchas Cohen is an advisor to and stockholder in CohBar Inc. UCLA has licensed the intellectual property on MOTS-c, on which Pinchas Cohen is listed as an inventor, to CohBar." PMID 29983246: "C.L. is a consultant for and a shareholder of CohBar, Inc." PMID 33473109: "P.C. and C.L. are consultants and shareholders of CohBar, Inc."18 iScience 20245 Cell Metab 201821 Nat Commun 20218 Elife 2026
  • Other studies on this page come from groups in China (Xi'an, Nanjing, Wuxi), South Korea (Seoul National University, with the USC group), Germany (German Sport University Cologne), Sweden (Karolinska Institutet), Spain (Catalan Institute of Oncology), Belgium (UCLouvain), New Zealand (University of Auckland) and the United States (Mayo Clinic, with the USC group); one more Chinese group is at Wenzhou Medical University. Source sentenceAffiliations: Fourth Military Medical University, Xi'an (29096170); Nanjing Medical University, affiliated hospital (40403491); Affiliated Hospital of Jiangnan University, Wuxi (42142418); Seoul National University College of Medicine (34320351); German Sport University Cologne (30394592); Karolinska Institutet (34351816); Catalan Institute of Oncology, Girona (36490309); UCLouvain (40674654); University of Auckland (42321010); Mayo Clinic, Rochester (42324588); Wenzhou Medical University (42153537)22 Mol Immunol 20179 Redox Biol 202519 Redox Biol 202623 Cell Rep 20217 Rapid Commun Mass Spectrom 201910 J Appl Physiol (1985) 202111 Aging (Albany NY) 202214 Med Sci Sports Exerc 202528 Exp Physiol 202629 Inflamm Regen 202630 Autophagy 2026
  • The one registered trial that gives MOTS-c is sponsored by a company, Hudson Biotech, with its listed site at Peking University Shenzhen Hospital in China. Source sentenceleadSponsor: Hudson Biotech (class INDUSTRY); location: Peking University Shenzhen Hospital, Shenzhen, Guangdong, China13 NCT07505745

Studies

  1. Analytical only (no biological model)Rapid Commun Mass Spectrom 2019

    LC/MS detection of MOTS-c, its metabolites and oxidation products in plasma, and comparison with ELISA levels in 20 healthy people

    Design
    Analytical method validation: liquid chromatography and mass spectrometry, compared with a commercial ELISA
    Population or model
    none (plasma assay, in vitro metabolism and stability)
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    Federal Ministry of the Interior - Federal Republic of Germany, Manfred-Donike Institute for Doping Analysis

    PubMed 30394592DOI

  2. In vitro or ex vivoCell Metab 2018

    Movement of MOTS-c into the nucleus after metabolic stress, nuclear gene expression and interaction with NRF2

    Design
    Cell culture: subcellular localisation, gene expression and protein interaction
    Population or model
    cultured cells under glucose restriction and metabolic stress
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    NIA NIH HHS

    One author declares being a consultant for and shareholder of CohBar, Inc.

    PubMed 29983246DOI

  3. RodentiScience 2024

    Binding of MOTS-c and K14Q MOTS-c to CK2, CK2 activity and glucose uptake in mouse muscle

    Design
    Cell-free binding and kinase assays, mouse study, human genetic association
    Population or model
    cell-free systems; mice; human carriers of the K14Q variant
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    NHLBI NIH HHS, NIA NIH HHS, NIGMS NIH HHS, NCI NIH HHS

    Pinchas Cohen declares being an advisor to and stockholder in CohBar Inc.; UCLA licensed the MOTS-c intellectual property, with Cohen as inventor, to CohBar.

    PubMed 39559755DOI

  4. RodentElife 2026

    Bacterial membrane measurements after MOTS-c exposure, MOTS-c expression in monocytes and bacterial counts in a mouse peritonitis model

    Design
    Antibacterial assays, monocyte and macrophage cell work, mouse peritonitis model
    Population or model
    E. coli and MRSA; human monocytes; primary mouse monocytes; mice with acute peritonitis
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    NIA NIH HHS, Pew Charitable Trusts, NIGMS NIH HHS

    Changhan Lee declares being a consultant and shareholder of CohBar, Inc.

    PubMed 42611943DOI

  5. RodentNat Commun 2021

    Physical performance in mice of three ages given MOTS-c, nuclear gene expression and MOTS-c in human muscle and blood after exercise

    Design
    Mouse study of three age groups, cell work and human exercise samples
    Population or model
    mice aged 2, 12 and 22 months; myoblasts; human skeletal muscle and plasma after exercise
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    NIA NIH HHS

    Pinchas Cohen and Changhan Lee declare being consultants and shareholders of CohBar, Inc.

    PubMed 33473109DOI

  6. RodentAging (Albany NY) 2021

    Disease prevalence by m.1382A>C genotype in three cohorts, glucose tolerance in mice given MOTS-c or K14Q MOTS-c, and insulin response measurements in cells

    Design
    Genetic association meta-analysis of three cohorts, mouse study and cell assays
    Population or model
    three Japanese cohorts (n = 27,527); male and female mice; cells
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    NIA NIH HHS, NIDDK NIH HHS, NCI NIH HHS, NIGMS NIH HHS

    Pinchas Cohen declares being a consultant and stockholder of CohBar Inc.

    PubMed 33468709DOI

  7. RodentCell Rep 2021

    Islet immune cell infiltration and T cell receptor and mTORC1 signalling in T cells

    Design
    Mouse model of autoimmune beta cell destruction, T cell transfer, ex vivo work on human T cells
    Population or model
    NOD mice; T cells from human donors
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    NIA NIH HHS, NIGMS NIH HHS

    PubMed 34320351DOIcorrection: 34525370

  8. RodentMol Immunol 2017

    Survival, bacterial load and cytokine levels in MRSA infected mice, and MAPK signalling in macrophages

    Design
    Mouse infection model and macrophage cell work
    Population or model
    mice infected with MRSA; macrophages
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact

    PubMed 29096170DOI

  9. RodentRedox Biol 2025

    Nuclear transport of MOTS-c with MYH9, binding at antioxidant gene promoters and lung injury measures in rats

    Design
    Rat lung ischaemia reperfusion model, endothelial cell work, human serum cohort after cardiopulmonary bypass
    Population or model
    rat lung ischaemia reperfusion models; endothelial cells
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact

    PubMed 40403491DOI

  10. RodentExp Physiol 2026

    NLRP3 inflammasome proteins in left ventricular tissue and plasma cytokines in rats given MOTS-c

    Design
    Rat model with plasma and heart tissue analysis
    Population or model
    streptozotocin-induced rat model
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact
    Funding
    Heart Foundation of New Zealand Research Fellowship, Emerging Research First Grants, Health Research Council of New Zealand, Auckland Medical Research Foundation

    PubMed 42321010DOI

  11. In vitro or ex vivoInflamm Regen 2026

    AMPK signalling, proliferation and senescence genes in human mesenchymal stromal cells exposed to MOTS-c, and kidney perfusion and injury in mice given pretreated cells

    Design
    Human cell culture and mouse renal artery stenosis model
    Population or model
    human mesenchymal stromal cells from 12 donors; mouse model of renal artery stenosis
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact

    One author declares advisory roles with CureSpec, LiveKidney.bio and Cellergy.

    PubMed 42324588DOI

  12. RodentAutophagy 2026

    Flap blood flow perfusion, histology, lysosomal membrane permeability, autophagy and pyroptosis markers and PLA2G4A signalling after MOTS-c

    Design
    Mouse ischaemic skin flap model with RNA sequencing, histology and endothelial cell work
    Population or model
    C57BL mice (MeSH); human umbilical vein endothelial cells
    Molecule
    MOTS-c (MRWQEMGYIFYPRKLR) exact

    PubMed 42153537DOI

  13. Human, randomisedJ Appl Physiol (1985) 2021

    Plasma and skeletal muscle MOTS-c in endurance, resistance and control groups

    Design
    Randomised exercise study (endurance, resistance or control); MOTS-c was measured, not given
    Population or model
    healthy adults, 10 per group
    Molecule
    Endogenous MOTS-c, measured in participants, not given related form
    n
    30
    Comparator
    no exercise control
    Funding
    NIA NIH HHS

    PubMed 34351816DOI

  14. Human, randomisedAging (Albany NY) 2022

    Circulating MOTS-c measured by competitive ELISA, with and without metformin

    Design
    Secondary analysis of a randomised trial of metformin added to neoadjuvant chemotherapy and trastuzumab; MOTS-c was measured, not given
    Population or model
    women with HER2-positive breast cancer
    Molecule
    Endogenous MOTS-c, measured in participants, not given related form
    Comparator
    same regimen without metformin

    PubMed 36490309DOI

  15. Human, randomisedMed Sci Sports Exerc 2025

    Circulating and skeletal muscle MOTS-c and FGF21 before and after immobilisation with heat or sham exposure

    Design
    Randomised heat or sham exposure study during ankle immobilisation; MOTS-c was measured, not given
    Population or model
    physically active men
    Molecule
    Endogenous MOTS-c, measured in participants, not given related form
    n
    19
    Comparator
    sham exposure

    PubMed 40674654DOI

  16. Human, uncontrolledExp Physiol 2026

    Plasma humanin, MOTS-c and SHMOOSE measured by in-house ELISA in the three study groups

    Design
    Exercise study in three groups (adults with cerebral palsy, typically developing adults and adolescents); MOTS-c was measured, not given
    Population or model
    adults with cerebral palsy and typically developing adults and adolescents
    Molecule
    Endogenous MOTS-c, measured in participants, not given related form
    Funding
    Promobilia Foundation, Swedish Society for Medical Research, Swedish Research Council, Linnea och Josef Carlssons Stiftelse, Elsass Foundation, Neuroförbundet, Sunnerdahls Disability Foundation, Norrbacka Eugenia Foundation, Swedish Society for Child Welfare, Sven Jerring Foundation, Karolinska Institutet, Swedish Order of Freemasons Stockholm Childrens Welfare Foundation, H.K.H. Kronprinsessan Lovisas Förening för Barnasjukvård, O.E and Edla Johanssons Science Foundation, Gustafssons Foundation, Tornspiran Foundation, Maja & J.P. Åhlén Foundation, Folke Bernadotte Foundation

    PubMed 42349896DOI

  17. Human, uncontrolledBiochim Biophys Acta Gen Subj 2022

    Muscle fibre type and leg strength by m.1382A>C genotype, and muscle myosin heavy chain expression in mice given a MOTS-c neutralising antibody

    Design
    Genetic association study in Japanese adults and athletes, with a mouse antibody experiment; MOTS-c was not given
    Population or model
    211 healthy Japanese adults; 86 young men; 721 athletes and 873 controls; mice given a MOTS-c neutralising antibody
    Molecule
    Endogenous MOTS-c and the K14Q variant (genotype), not given related form
    Funding
    NIA NIH HHS

    Pinchas Cohen declares being a consultant and stockholder of CohBar Inc.

    PubMed 34728329DOI

  18. RodentRedox Biol 2026

    Cell uptake through LAT1, Nrf2 signalling and lung injury measures for R13A-MOTS-c

    Design
    Cell uptake assays and mouse radiation lung injury model with an engineered analogue
    Population or model
    MLE-12 cells; C57BL/6 mice after thoracic irradiation
    Molecule
    R13A-MOTS-c (arginine 13 replaced by alanine), an engineered analogue related form

    PubMed 42142418DOI

Mechanisms studied

  • The 2015 discovery paper studied skeletal muscle as the main target tissue and measured de novo purine biosynthesis and AMPK activation in cells. Source sentenceIts primary target organ appears to be the skeletal muscle, and its cellular actions [...] its tethered de novo purine biosynthesis, leading to AMPK activation.1 Cell Metab 2015
  • In cultured cells, a 2018 study traced MOTS-c into the nucleus after metabolic stress and measured nuclear gene expression and its interaction with the transcription factor NRF2. Source sentenceMOTS-c, a peptide encoded in the mitochondrial genome, translocates to the nucleus [...] following metabolic stress [...] interacted with ARE-regulating stress-responsive transcription factors, such as nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2)5 Cell Metab 2018
  • A 2024 study measured direct binding of MOTS-c to the kinase CK2 and CK2 activity in cell-free systems, then CK2 activity and glucose uptake in mouse skeletal muscle. Source sentenceMOTS-c directly binds to CK2 and activates it in cell-free systems. MOTS-c administration to mice [...] muscle glucose uptake18 iScience 2024
  • A 2026 study measured bacterial membrane properties of Escherichia coli and MRSA after MOTS-c exposure, MOTS-c expression in human monocytes after interferon gamma or LPS, and bacterial counts in a mouse peritonitis model; the authors describe it as a host defence peptide. Source sentenceMOTS-c targeted Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), in part, by targeting their membranes [...] In a mouse model of acute peritonitis [...] In human monocytes, interferon gamma (IFNγ), lipopolysaccharides (LPS), and differentiation signals each induced the expression of endogenous MOTS-c8 Elife 2026
  • A 2025 rat lung ischaemia reperfusion study measured MOTS-c moving into the nucleus with MYH9 and binding at promoters of antioxidant genes such as HMOX1 and NQO1. Source sentenceIn rat LIRI models [...] enabling MOTS-c binding to MYH9-γ-Actin complexes for nuclear transport [...] direct MOTS-c interaction with promoters of antioxidant genes (e.g., HMOX1, NQO1)9 Redox Biol 2025
  • A 2021 study in a mouse model of autoimmune beta cell destruction measured islet immune cell infiltration and T cell receptor and mTORC1 signalling in T cells, including T cells from human donors. Source sentenceprevented autoimmune β cell destruction by targeting T cells [...] reduced islet-infiltrating immune cells [...] MOTS-c modulated T cell phenotype and function by regulating T cell receptor (TCR)/mTOR complex 1 (mTORC1) signaling [...] in T1D patients23 Cell Rep 2021
  • A 2021 study measured physical performance in mice aged 2, 12 and 22 months given MOTS-c, and MOTS-c in human skeletal muscle and blood after exercise. Source sentencephysical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice [...] In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation21 Nat Commun 2021
  • A 2026 rat study measured NLRP3 inflammasome proteins (NLRP3, ASC and cleaved caspase-1) in heart tissue and plasma cytokines in a streptozotocin-induced metabolic disease model given MOTS-c. Source sentenceNLRP3) inflammasome activity in a [...] streptozotocin-induced T2DM rat model [...] Immunohistochemical analysis revealed [...] levels of NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and cleaved caspase-1 in left ventricular tissue28 Exp Physiol 2026
  • A 2026 study measured AMPK signalling, proliferation and the senescence genes p16 and p21 in human mesenchymal stromal cells exposed to MOTS-c, and kidney perfusion, fibrosis and tubular injury in mice given MOTS-c pretreated cells. Source sentenceassessed in vitro for changes in proliferation, senescence (p16, p21) TNF-α, and antioxidant gene expression following MOTS-c co-incubation [...] activated AMPK signaling [...] in a murine model of renal artery stenosis, MOTS-c-pretreated MSCs [...] renal perfusion, fibrosis, or tubular injury29 Inflamm Regen 2026
  • A 2026 mouse study of ischaemic skin flaps measured blood flow perfusion, lysosomal membrane permeability, autophagy and pyroptosis markers and PLA2G4A phosphorylation after MOTS-c, with endothelial cell work. Source sentenceTissue clearing, laser speckle contrast imaging and Doppler analyses [...] blood flow perfusion [...] Western blotting, ELISA, and immunofluorescence were used to assess pyroptosis, macroautophagy/autophagy, LMP, and MAPK1/ERK2-MAPK3/ERK1-NFKB/NF-κB pathway-related proteins [...] PLA2G4A phosphorylation30 Autophagy 2026

Status matrix

United States: FDA records

US

  • The FDA records below concern bulk drug substances nominated for use in pharmacy compounding under section 503A of the Federal Food, Drug, and Cosmetic Act. Source sentenceBulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act33 FDA, 503A bulk drug substance categories, updated 14 May 2026
  • FDA's Category 2 page lists MOTs-C, its spelling for MOTS-c, under bulk drug substances nominated but withdrawn, substances that were previously in category 2 and whose nominations were withdrawn by the nominators (content current as of 22 Apr 2026). Withdrawn by the nominator is not approval and not listing. Source sentenceBulk drug substances nominated but withdrawn This list of bulk drug substances previously in category 2 of the interim policies were withdrawn by the nominators. ... MOTs-C ... Content current as of: 04/22/202625 FDA, bulk drug substances Category 2 page, content current as of 22 April 2026
  • For MOTs-C FDA states that it "has not identified any human exposure data on drug products containing MOTs-C" and that it "lacks important information regarding any safety issues raised by MOTs-C". Source sentenceFDA has not identified any human exposure data on drug products containing MOTs-C administered via any route of administration. FDA lacks important information regarding any safety issues raised by MOTs-C, including whether it would cause harm if administered to humans.25 FDA, bulk drug substances Category 2 page, content current as of 22 April 2026
  • MOTS-c does not appear in FDA's list of bulk drug substances nominated under section 503A, updated 14 May 2026, which holds categories 1, 2 and 3. Source sentenceUpdated May 14, 2026 ... Includes three categories of bulk drug substances: Category 1: Bulk Drug Substances Under Evaluation; Category 2: Bulk Drug Substances that Raise Significant Safety Concerns; Category 3: Bulk Drug Substances Nominated Without Adequate Support (text search for MOTS, MOT and 12S: no match)33 FDA, 503A bulk drug substance categories, updated 14 May 2026
  • A Federal Register notice of 16 Apr 2026 (docket FDA-2025-N-6895) listed "MOTs-C-related bulk drug substances (MOTs-C (free base)/MOTs-C acetate)" for discussion by the Pharmacy Compounding Advisory Committee on 23 Jul 2026, among substances being considered for the 503A bulks list. Source sentenceOn July 23, 2026, the Committee will discuss the following bulk drug substances being considered for inclusion on the 503A Bulks List: ... and MOTs-C-related bulk drug substances (MOTs-C (free base)/MOTs-C acetate)26 Federal Register 2026-07361, 16 April 2026
  • No FDA approved drug containing MOTS-c was found in openFDA Drugs@FDA on 25 Oct 2026. Source sentenceNOT_FOUND: No matches found!24 openFDA Drugs@FDA query for MOTS-c, 25 October 2026
  • FDA's substance registry (GSRS, UNII A5CV6JFB78) records the substance as mitochondria-derived peptide MOTS-c with CAS 1627580-64-6, PubChem CID 146675088 and the sequence MRWQEMGYIFYPRKLR. Source sentence_name: MITOCHONDRIA-DERIVED PEPTIDE MOTS-C; names: MOTS-C; codes: CAS 1627580-64-6, PUBCHEM 146675088, FDA UNII A5CV6JFB78; subunit sequence MRWQEMGYIFYPRKLR34 FDA Global Substance Registration System, UNII A5CV6JFB78

Sport anti-doping list

International

  • The WADA 2026 Prohibited List names MOTS-c, written as mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), in class S4.4.1 among activators of the AMP-activated protein kinase (AMPK), under S4 Hormone and metabolic modulators, prohibited at all times, in and out of competition. Source sentenceS4 HORMONE AND METABOLIC MODULATORS PROHIBITED AT ALL TIMES (IN- AND OUT-OF-COMPETITION) ... S4.4.1 Activators of the AMP-activated protein kinase (AMPK), e.g. ... AICAR, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)27 WADA Prohibited List 2026
  • The list states that substances in classes S4.3 and S4.4 are non-Specified Substances. Source sentenceThose in classes S4.3 and S4.4 are non-Specified Substances.27 WADA Prohibited List 2026
  • Anti-doping laboratory work names MOTS-c: a 2016 review from the German Sport University Cologne listed it among emerging substances relevant to sports drug testing, and a 2019 study from the same centre validated an LC/MS method for MOTS-c in plasma according to WADA's International Standard for Laboratories. Source sentencePMID 30394592: "The LC/MS-based test method was fully validated for quantitative results interpretation according to the World Anti-Doping Agency's International Standard for Laboratories (WADA's ISL)." PMID 26842585: "Substances of interest include" [...] "(MOTS-c)" in a review of substances "which might become relevant for doping controls in the future"7 Rapid Commun Mass Spectrom 201935 Rapid Commun Mass Spectrom 2016

Registered trials

  • NCT07505745Phase 2

    Status
    Recruiting (start 2 Feb 2026, estimated primary completion 14 Feb 2027)
    Sponsor
    Hudson Biotech
    Site countries
    China (global context)
    Primary endpoint
    change from baseline in OGTT-derived insulin sensitivity (Matsuda index); incidence of treatment-emergent adverse events
    Primary endpoint met
    not reported
    Last synced
    25 October 2026
  • ClinicalTrials.gov on 25 Oct 2026: 9 records for "MOTS-c" and the same 9 for "MOTS c", none for "MOTSc". One gives MOTS-c (NCT07505745); five list MOTS-c levels as a measure or marker (NCT07438002, NCT04027712, NCT03878706, NCT04013568, NCT07678073); three do not mention MOTS-c in their record text. Source sentencetotalCount: MOTS-c 9; MOTS c 9; MOTSc 0; record text mentions MOTS-c in NCT07505745, NCT07438002, NCT04027712, NCT03878706, NCT04013568, NCT07678073; no mention in NCT06133946, NCT07638696, NCT0650097512 ClinicalTrials.gov search, 25 October 202613 NCT07505745

Timeline

  1. A 16 amino acid peptide encoded in the mitochondrial 12S rRNA is reported and named MOTS-c Source sentenceCell Metab 2015: "a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c"1 Cell Metab 2015
  2. The m.1382A>C variant in the MOTS-c coding region is described as specific to Northeast Asian populations Source sentenceAging Cell 2015: "the m.1382A>C polymorphism located in the MOTS-c encoding mtDNA, which is specific for the Northeast Asian population"3 Aging Cell 2015
  3. Movement of MOTS-c into the nucleus after metabolic stress measured in cells Source sentenceCell Metab 2018: translocates to the nucleus [...] following metabolic stress5 Cell Metab 2018
  4. LC/MS doping control method for MOTS-c in plasma validated Source sentenceRapid Commun Mass Spectrom 2019: assay comprehensively validated, compared with a commercial ELISA7 Rapid Commun Mass Spectrom 2019
  5. Physical performance measured in mice of three ages given MOTS-c Source sentenceNat Commun 2021: young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice21 Nat Commun 2021
  6. Direct binding of MOTS-c to the kinase CK2 measured Source sentenceiScience 2024: MOTS-c directly binds to CK2 [...] in cell-free systems18 iScience 2024
  7. A phase 2 trial that gives MOTS-c starts recruiting in China Source sentenceStudy start 2026-02-02 (actual); overall status Recruiting; location China; phase PHASE213 NCT07505745
  8. Peer reviewed version of the host defence peptide study published Source sentenceeLife, electronic date 2026-08-18; PubMed UpdateOf 395539718 Elife 2026

Integrity notes

  • PubMed CommentsCorrections and Crossref update-to were checked on 25 Oct 2026 for the studies and reviews used as evidence on this page: one published erratum was found (PMID 34525370, for the 2021 mouse T cell study, PMID 34320351), and no retraction or expression of concern. Source sentencePMID 34320351 CommentsCorrections: ErratumIn 34525370; Crossref: 10.1016/j.celrep.2021.109724 is an erratum to 10.1016/j.celrep.2021.109447; no retraction or expression of concern entries for the other cited PMIDs on 25 Oct 202623 Cell Rep 202136 Cell Rep 2021
  • One MOTS-c paper in the PubMed set is retracted: a 2019 study on bone marrow mesenchymal stem cells in Eur Rev Med Pharmacol Sci was withdrawn in 2021 "due to inaccuracies during the process of organizing the images", as its retraction notice states (PMID 33829422). It is not used as evidence on this page. Source sentencehas been withdrawn from the authors due to inaccuracies during the process of organizing the images37 Eur Rev Med Pharmacol Sci 2021
  • The 2026 eLife host defence paper (PMID 42611943) is the peer reviewed version of a bioRxiv preprint indexed in PubMed in 2024 (PMID 39553971); this page cites the eLife version. Source sentencePMID 42611943 CommentsCorrections: UpdateOf 39553971; PMID 39553971 publication types: Journal Article, Preprint; journal bioRxiv8 Elife 202638 bioRxiv 2024

Chemistry and records

MOTS-c: sequence, mass, CAS and regulatory record in the research library →

Sources

  1. 1Cell Metab 2015 accessed 25 Oct 2026
  2. 2PubChem CID 146675088 accessed 25 Oct 2026
  3. 3Aging Cell 2015 accessed 25 Oct 2026
  4. 4Sports Med 2026 accessed 25 Oct 2026
  5. 5Cell Metab 2018 accessed 25 Oct 2026
  6. 6PubMed search for MOTS-c, 25 October 2026 accessed 25 Oct 2026
  7. 7Rapid Commun Mass Spectrom 2019 accessed 25 Oct 2026
  8. 8Elife 2026 accessed 25 Oct 2026
  9. 9Redox Biol 2025 accessed 25 Oct 2026
  10. 10J Appl Physiol (1985) 2021 accessed 25 Oct 2026
  11. 11Aging (Albany NY) 2022 accessed 25 Oct 2026
  12. 12ClinicalTrials.gov search, 25 October 2026 accessed 25 Oct 2026
  13. 13NCT07505745 accessed 25 Oct 2026
  14. 14Med Sci Sports Exerc 2025 accessed 25 Oct 2026
  15. 15Exp Physiol 2026 accessed 25 Oct 2026
  16. 16Peptency catalog chemistry record, MOTS-c accessed 25 Oct 2026
  17. 17Aging (Albany NY) 2021 accessed 25 Oct 2026
  18. 18iScience 2024 accessed 25 Oct 2026
  19. 19Redox Biol 2026 accessed 25 Oct 2026
  20. 20ACS Chem Neurosci 2021 accessed 25 Oct 2026
  21. 21Nat Commun 2021 accessed 25 Oct 2026
  22. 22Mol Immunol 2017 accessed 25 Oct 2026
  23. 23Cell Rep 2021 accessed 25 Oct 2026
  24. 24openFDA Drugs@FDA query for MOTS-c, 25 October 2026 accessed 25 Oct 2026
  25. 25FDA, bulk drug substances Category 2 page, content current as of 22 April 2026 accessed 25 Oct 2026
  26. 26Federal Register 2026-07361, 16 April 2026 accessed 25 Oct 2026
  27. 27WADA Prohibited List 2026 accessed 25 Oct 2026
  28. 28Exp Physiol 2026 accessed 25 Oct 2026
  29. 29Inflamm Regen 2026 accessed 25 Oct 2026
  30. 30Autophagy 2026 accessed 25 Oct 2026
  31. 31Peptency Academy sourcing policy, version 1 accessed 25 Oct 2026
  32. 32Biochim Biophys Acta Gen Subj 2022 accessed 25 Oct 2026
  33. 33FDA, 503A bulk drug substance categories, updated 14 May 2026 accessed 25 Oct 2026
  34. 34FDA Global Substance Registration System, UNII A5CV6JFB78 accessed 25 Oct 2026
  35. 35Rapid Commun Mass Spectrom 2016 accessed 25 Oct 2026
  36. 36Cell Rep 2021 accessed 25 Oct 2026
  37. 37Eur Rev Med Pharmacol Sci 2021 accessed 25 Oct 2026
  38. 38bioRxiv 2024 accessed 25 Oct 2026

About this page

Research-use information. This library summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.

Reviewed by the Peptency editorial process. Version 1, last edited 25 October 2026, 38 sources.

Cite this page: Peptency Academy. MOTS-c: mitochondrial peptide chemistry, studies and status. Version 1./us/academy/compounds/mots-c/