MOTS-c

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

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

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.

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.