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Research

MOTS-c — living evidence map

The Atlas page holds the claims; this is how its evidence evolved.

Summary

Mitochondrial open reading frame of the 12S rRNA-c: a sixteen-amino-acid peptide encoded inside mitochondrial DNA rather than the nucleus - a peptide the mitochondrion writes itself. · seed: prototype 03 (2026-09-19), identifiers as printed t...

Classification

Mitochondrial-derived peptide (MDP): a short-ORF product of the mitochondrial 12S rRNA locus. · seed: prototype 03 (2026-09-19), identifiers as printed t...

Mechanism

Reported to modulate the folate cycle and AICAR-dependent AMPK activation, with skeletal muscle the apparent principal site of action (Lee C et al., 2015). · seed: prototype 03 (2026-09-19), identifiers as printed t...

Under metabolic stress MOTS-c translocates to the nucleus in an AMPK-dependent manner and regulates nuclear genes, including those with antioxidant response elements. · pmid:29983246

History

First described in 2015 (Lee C et al., Cell Metab), as a mitochondrial signal regulating insulin sensitivity and metabolic homeostasis. · seed: prototype 03 (2026-09-19), identifiers as printed t...

It enhanced physical performance in young, middle-aged and old mice, and in humans exercise induced MOTS-c expression in skeletal muscle and in the circulation. · pmid:33473109

Identity

Mitochondrial-derived peptide MOTS-c. UniProt A0A0C5B5G6 (MOTSC_HUMAN), 16 residues, Homo sapiens · uniprot:A0A0C5B5G6

PubChem CID 146675088: Mots-c, C101H152N28O22S2, 2174.6 g/mol. · pubchem:146675088

CAS registry number 1627580-64-6. · pubchem:146675088

Where the evidence actually sits

Established25%
Emerging25%
Preclinical only50%

Proportion of the 8 claims about MOTS-c standing at each tier. Community volume is shown on the Consensus tab beside this and is never averaged into it.

Living evidence history

The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. (2015) · establishedThe mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. (2015) · establishedThe Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. (2018) · preclinicalMOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. (2021) · preclinicalThe mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. (2022) · preclinicalMOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. (2022) · emergingRole of MOTS-c in the regulation of bone metabolism. (2023) · emergingMitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination. (2024) · preclinical20152024

8 resolved citations, oldest to newest, coloured by tier. Retractions and contradictions land here as they are recorded.

Structure

Primary structure, N-terminus to C-terminus: 16 residues as the record states them. No 2D or 3D depiction is on record; none is guessed.

1 methionine (Met), hydrophobicMet12 arginine (Arg), basicArg23 tryptophan (Trp), aromaticTrp34 glutamine (Gln), polarGln45 glutamate (Glu), acidicGlu56 methionine (Met), hydrophobicMet67 glycine (Gly), specialGly78 tyrosine (Tyr), aromaticTyr89 isoleucine (Ile), hydrophobicIle910 phenylalanine (Phe), aromaticPhe1011 tyrosine (Tyr), aromaticTyr1112 proline (Pro), specialPro1213 arginine (Arg), basicArg1314 lysine (Lys), basicLys1415 leucine (Leu), hydrophobicLeu1516 arginine (Arg), basicArg16NC
acidic aromatic basic hydrophobic polar special

Source uniprot:A0A0C5B5G6, fetched not recalled. Side-chain classes are the textbook classes of the standard residues.

Dose evidence, rung by rung

A studied human dose exists on file. Open the rung: the dose is the paper's, in its context, never PepJunkie's.

  1. Approved-label dose · a resolved regulatory document names a labelled dose

    nothing resolved on this rung

  2. Studied human doses · resolved human studies at the established tier
    • The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. · pmid 25738459 · 2015
    • The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. · pmid 25738459 · 2015
  3. Observational evidence · resolved human data at the emerging tier: thin, or contested
    • MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. · pmid 36233287 · 2022
    • Role of MOTS-c in the regulation of bone metabolism. · pmid 37200834 · 2023
  4. Community-reported protocols · protocol propositions from distinct members, counted once per human

    nothing resolved on this rung

  5. Preclinical evidence · resolved animal, cell or mechanistic work
    • The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. · pmid 29983246 · 2018
    • MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. · pmid 33473109 · 2021
    • The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. · pmid 34798268 · 2022
    • Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination. · pmid 39321430 · 2024

8 resolved citations, 0 unresolved (an unresolved citation lends nothing). Community volume is its own rung and is never averaged into the evidence rungs.