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Research library, Mitochondria-encoded 16-residue peptide

MOTS-c: chemistry, literature and regulatory status

Written by the Peptency editorial teamLast reviewed 4 studies checked in PubMed on 5 October 2026

Research-use information. This page 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.

What is MOTS-c?

MOTS-c is a 16-residue peptide encoded by a short open reading frame in the mitochondrial 12S rRNA gene. Research describes it as a mitochondrial-derived signalling peptide that can enter the nucleus under metabolic stress. It is supplied here as a research material for laboratory use only.

What are the chemical facts for MOTS-c?

Name
MOTS-c
Also written
Mitochondrial ORF of the 12S rRNA-c
Sequence
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
Length
16 residues
Molecular formula
C101H152N28O22S2 (matches the formula computed from the sequence)
Average molecular weight
2174.6 g/mol
CAS number
1627580-64-6 (confirmed in PubChem)
PubChem
CID 146675088

Chemistry checked against PubChem on 2026-10-05. Where the formula can be computed from the listed sequence, it was, and the two routes agree.

How does the literature describe the mechanism of MOTS-c?

  • The discovery paper identified the open reading frame in mitochondrial DNA and reported metabolic effects in cells and mice.[4]
  • MOTS-c was shown to translocate to the nucleus in response to metabolic stress and to regulate nuclear gene expression.[2]
  • A 2026 paper identifies MOTS-c as a mitochondria-encoded host defense peptide with interferon-linked activity.[1]

Receptor and pathway background: Mitochondria-linked peptides.

What has published research on MOTS-c looked at?

4 studies are cited for MOTS-c. Each is labelled by design below, and each entry says what the paper measured.

  • 3 in vitro and animal study
  • 1 review

PubMed returns 262 records for the search terms published on the method page (57 of them with a review publication type, 8 with a clinical-trial publication type), checked 5 October 2026. ClinicalTrials.gov lists 5 registered studies whose intervention matches the name (2 interventional), checked 5 October 2026.

  • A 2016 review describes MOTS-c as a mitochondrial-derived peptide in muscle and fat metabolism.[3]

Studies are listed by what they measured. Papers whose titles state an amount or schedule, or describe a clinical outcome of an approved medicine, are not listed. This is a wording rule, not a quality filter; see the method page.

What is the regulatory status of MOTS-c?

FDA

No application listed

No application naming MOTS-c as an active ingredient is listed in Drugs@FDA. Checked 2026-10-05; the control lookup (semaglutide) returned 6 applications.

Drugs@FDA via openFDA

EMA

No centrally authorised medicine listed

No centrally authorised procedure in the EMA medicines database (checked 5 October 2026) names MOTS-c as an active substance. National authorisations are not in this dataset.

EMA medicines data

MHRA

No product document found

No SmPC, PIL or PAR document in MHRA Products matches the exact name "MOTS-c". Checked 2026-10-05; the control lookup (semaglutide) returned 271 documents.

MHRA Products

WADA

Named, S4.4

The WADA 2026 Prohibited List, in force 1 January 2026 names MOTS-c under S4.4 (metabolic modulators). A WADA entry is a sporting rule, not a statement about legality outside sport.

WADA Prohibited List 2026

A regulator record is information about a database entry. It is not advice and not a statement that any use is lawful or unlawful in any country. How regulators approach research peptides.

Data dates: regulatory records 2026-10-05; WADA list 2026-10-05.

Which studies are cited for MOTS-c?

  1. [1] Rice MC, Imun M, Jung SW, Park CY, Kim JS, Lai RW, et al.. MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide. Elife. 2026;12.

    Identified MOTS-c as a mitochondria-encoded host defense peptide and tested its antimicrobial and interferon-linked activity.

    In vitro and animal studyPMID 42611943DOI 10.7554/eLife.87615
  2. [2] Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018;28:516-524.e7.

    Showed that MOTS-c translocates to the nucleus under metabolic stress and regulates nuclear gene expression.

  3. [3] Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016;100:182-187.

    Review of MOTS-c as a mitochondrial-derived peptide in muscle and fat metabolism.

  4. [4] Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, et al.. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21:443-54.

    Identified the MOTS-c open reading frame in mitochondrial DNA and reported its metabolic effects in cells and mice.

Data dates: citations read from PubMed 2026-10-05.

Where else in the research library is MOTS-c covered?

Who wrote this page and how is it checked?

Peptency editorial team, last reviewed 5 October 2026. Citations are read back from PubMed, chemistry is checked against PubChem, and regulator records are read from each regulator's own database on the dates shown. The method page lists every source, search term and rule. Corrections are welcome through the contact details on the About page.