MOTS-c: clinical evidence record
Also known as: Mitochondrial Open Reading Frame of the 12S rRNA-c, MOTSc
Oliver Mackman · Editorial director · Best Business Loans Ltd (16833937)
Last updated 2026-05-22
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AI-friendly summary · MOTS-c
Discovered by the Cohen lab at USC in 2015. Preclinical mouse evidence for AMPK activation, insulin sensitisation, and exercise capacity. Early-phase human pharmacokinetic and pilot-study work has begun. No phase III human RCTs published.
Mechanism of action
How MOTS-c works
16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA region of mitochondrial DNA. Proposed to activate AMP-activated protein kinase (AMPK), regulate metabolic homeostasis, and influence glucose uptake and insulin sensitivity in preclinical models.
Top peer-reviewed citations
Selection of the most-cited peer-reviewed literature on MOTS-c. Where a verified PMID or DOI is shown, the citation links to the original record. Other citations list the title, authors, journal and year so the reader can locate the paper through the journal index or the PubMed search linked below. PeptideClear publishes editorial commentary, not clinical guidance.
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The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis
Lee C, Zeng J, Drew BG, et al.. Cell Metabolism, 2015.
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MOTS-c is an exercise-induced mitochondrial-encoded regulator
Reynolds JC, Lai RW, Woodhead JST, et al.. Nature Communications, 2021.
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MOTS-c and insulin sensitivity in humans
Ramanjaneya M, Bettahi I, Jerobin J, et al.. Frontiers in Endocrinology, 2019.
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Mitochondrial-derived peptides and ageing
Yen K, Mehta HH, Kim SJ, et al.. Aging, 2020.
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MOTS-c administration and physical performance in mice
Reynolds JC, Lai RW, Woodhead JST, et al.. Nature Communications, 2021.
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Mitochondrial-derived peptides in metabolic disease
Merry TL, Chan A, Woodhead JST, et al.. American Journal of Physiology Endocrinology and Metabolism, 2020.
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Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals
Cataldo LR, Fernandez-Verdejo R, Santos JL, Galgani JE. Journal of Investigative Medicine, 2018.
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Mitochondrially derived peptides as novel regulators of metabolism
Kim SJ, Xiao J, Wan J, Cohen P, Yen K. The Journal of Physiology, 2017.
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MOTS-c regulates folate cycle and methionine metabolism
Kim KH, Son JM, Benayoun BA, Lee C. Cell Metabolism, 2018.
Full PubMed search: https://pubmed.ncbi.nlm.nih.gov/?term=MOTS-c+mitochondrial+peptide.
UK regulatory status
Plain-English summary of where MOTS-c sits under the four UK and international frameworks that govern peptide supply. Editorial commentary, not legal advice.
- Misuse of Drugs Act 1971: Not controlled under the Misuse of Drugs Act 1971.
- Psychoactive Substances Act 2016: Not scheduled under the Psychoactive Substances Act 2016.
- MHRA medicines classification: No UK marketing authorisation as a medicine.
- WADA Prohibited List: WADA Prohibited List S4 (hormone and metabolic modulators), prohibited at all times.
Full regulatory record: MOTS-c UK regulatory status.
Risks and unknowns
What the literature does not yet show about MOTS-c
Known concerns
- Most published efficacy claims for MOTS-c require careful interpretation. Read the cited papers in full before drawing conclusions.
- Purity of UK research-peptide supply varies between retailers. Certificates of analysis and HPLC documentation differ.
- Cold-chain handling between manufacture and delivery is not standardised across the research-peptide market.
- Independent replication of single-group findings is the key check on any preclinical claim.
Open questions in the literature
- Where human pharmacokinetics have not been formally characterised, dose translation from animal models is not reliable.
- Long-term safety profile beyond the duration of published studies remains an open question.
- Interactions with other prescribed or unlicensed substances are typically not studied.
Regulatory note
No UK marketing authorisation as a medicine. Prohibited at all times under WADA S4 (hormone and metabolic modulators). The moment a UK seller or commentator makes a therapeutic claim, MHRA can treat the product as an unlicensed medicinal product.
Important: PeptideClear publishes encyclopedia commentary only and does not recommend human use. Speak to a UK-registered prescriber before any medical decision.
Related reading on PeptideClear
Frequently asked questions
What is the evidence level for MOTS-c?
What is the UK regulatory status of MOTS-c?
Has MOTS-c been tested in human clinical trials?
Where can I read the source literature for MOTS-c?
Last verified 2026-05-22. Editorial commentary, not legal or clinical advice. Citations without a linked identifier can be located through the PubMed search and the journal index.