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PeptideHormone

MOTS-c

A mitochondrial-encoded peptide linked to metabolism and exercise biology.

EndogenousPreclinicalCompounding restricted

Encoded by the mitochondrion rather than the nucleus. The cell's other genome turns out to be writing signals of its own.

Identity

Class
Mitochondrial-derived peptide (16 aa, encoded in 12S rRNA)
Source
Encoded in mitochondrial DNA
Receptor
No classical receptor; acts via AMPK and metabolic signaling

Key properties

Evidence floorCommunityREF1COMM1
Molecular weight
~2,174.6 Da
REF
Half-life (native)
Poorly characterized (short in circulation)
COMMHalf-life is poorly characterized in humans. The figure is indicative of order-of-magnitude, not an established value.

Approximate values for the native hormone; engineered analogs are often deliberately larger and far longer-acting. Each figure carries its own provenance tier, and the floor is the weakest of them - the Standard.

Mechanism

MOTS-c is a short peptide encoded within mitochondrial DNA that signals to the rest of the cell, acting partly through AMPK to influence glucose metabolism and insulin sensitivity. In animal studies it behaves as an exercise-mimetic, though human evidence remains early.

Reference notes

  • It is encoded in mitochondrial — not nuclear — DNA, an unusual origin for a signaling peptide.
  • It acts substantially through AMPK and metabolic-stress pathways rather than a single surface receptor.
  • Evidence is largely preclinical; human metabolic roles are still being mapped.

Regulatory status

United States · reviewed September 2026
Compounding restrictedMOTS-c is an unapproved substance the FDA has placed in Category 2 of its 503A bulk-substances list, citing significant safety risks, so it may not lawfully be compounded.
Basis
FDA 503A bulk-substances list, Category 2 (substances that may present significant safety risks), September 2023. In July 2026 the Pharmacy Compounding Advisory Committee voted 7–5 with two abstentions to recommend adding it to the 503A list, against FDA staff advice; the vote is non-binding and the status stands pending rulemaking.

Status describes the molecule as a drug substance under US law and is an editorial reading of the public record — approvals, trial registrations, and the FDA 503A bulk-substances list. It is not legal advice and it changes; the review date above is the last time the table was checked. Other jurisdictions are noted only where they differ materially.

Common questions

What is MOTS-c?
A mitochondrial-encoded peptide linked to metabolism and exercise biology. Structurally it is Mitochondrial-derived peptide (16 aa, encoded in 12S rRNA).
How does MOTS-c work?
MOTS-c is a short peptide encoded within mitochondrial DNA that signals to the rest of the cell, acting partly through AMPK to influence glucose metabolism and insulin sensitivity. In animal studies it behaves as an exercise-mimetic, though human evidence remains early.
How strong is the evidence for MOTS-c?
PeptideHormone grades MOTS-c at the "Preclinical" evidence tier — the evidence is largely animal or in-vitro, with human data thin or absent. It is catalogued as an endogenous signal the body produces itself, and the tier is an editorial judgment about the public literature that can change as the science does.
What is the half-life of MOTS-c?
The reported circulating half-life of MOTS-c is Poorly characterized (short in circulation).
Is MOTS-c FDA-approved?
No — as of September 2026, MOTS-c is an unapproved substance the FDA has placed in Category 2 of its 503A bulk-substances list, citing significant safety risks, so it may not lawfully be compounded. FDA 503A bulk-substances list, Category 2 (substances that may present significant safety risks), September 2023. In July 2026 the Pharmacy Compounding Advisory Committee voted 7–5 with two abstentions to recommend adding it to the 503A list, against FDA staff advice; the vote is non-binding and the status stands pending rulemaking. Status is US-centric and can change; check the FDA record for the current position.

In the literature

Live registry counts · retrieved
Registered trialsREF
43 recruiting
  • Ph 10
  • Ph 21
  • Ph 30
  • Ph 40
Open on ClinicalTrials.gov
PubMed recordsREF
255
Since 2022175 · 69%
Open on PubMed

Searched as MOTS-c. Counts are search hits from the primary registries, not a curated set and not a grade – a measure of how much work exists on MOTS-c, not how it turned out.

Selected literature

Curated peer-reviewed reviews, sourced from PubMed. Selected for relevance, not exhaustive — open any entry on PubMed for the full record and its primary citations.

  1. 1.MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation · Frontiers in endocrinology, 2023 · PMID 36761202
  2. 2.MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases · International journal of molecular sciences, 2022 · PMID 36233287

External references

MOTS-c in the public knowledge graph — the same entity resolved across the authoritative chemistry and protein databases.