What Is MOTS-c? The Mitochondrial-Derived Peptide

Name and origin

MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c. The name describes a short open reading frame associated with mitochondrial 12S ribosomal RNA, not a commercial effect.¹

This page answers “what is it.” It does not treat exercise as a therapy, does not summarize an insulin result in people, and does not interpret compounding. Those questions have their own pages in the MOTS-c research hub.

Sixteen amino acids

Sixteen residues define the usual length used in the discovery literature. That figure is a property of the sequence, not a dose and not an indication.¹

A certificate of analysis that reproduces sixteen residues is speaking about analytical identity. That match does not carry a metabolic outcome in people with it.

Mitochondrial 12S rRNA context

Unlike most research peptides, MOTS-c is described as associated with the mitochondrial genome, specifically a short frame of 12S rRNA. That location is why it appears in literature on signaling between mitochondrion and nucleus.^1,2

The genomic context does not make the peptide a medicine. It says where the sequence was read, not what it does in a patient.

Sequence

The usual one-letter sequence is MRWQEMGYIFYPRKLR. FDA’s substance record represents the corresponding sequence as Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg.^1,8

Those two notations name the same sixteen-residue chain. UNII availability does not imply regulatory review or approval. FDA’s own record says so.⁸

What a mitochondrial-derived peptide is

“Mitochondrial-derived peptide” — MDP — is a descriptive category. It groups short peptides associated with mitochondrial DNA. MOTS-c is one of them. Humanin appears in the same conceptual family in studies that measure several MDPs at once.^1,4

The category does not imply a shared clinical effect. It also does not make every product that uses the word “mitochondrial” in marketing equivalent.

Discovery

Lee and colleagues published the discovery paper in Cell Metabolism in 2015. They identified the short frame, the 16-amino-acid peptide, and a metabolic research line with a skeletal-muscle emphasis.¹

That paper also reported folate and purine findings and AMPK activation in models. The obesity and insulin-resistance intervention findings were largely preclinical. They are not read here as demonstrated human outcomes.¹

What has been studied

• Identity and mitochondrial origin of the peptide.¹
• Cellular mechanisms, including translocation to the nucleus under metabolic stress.²
• Administration in mice in metabolic and physical-capacity models.^1,3
• Measurements of endogenous MOTS-c in people, especially around exercise.^3,4
• A Phase 2a trial that now administers the investigational peptide to participants.⁵

Mechanism is developed in AMPK, mitochondria, and proposed mechanisms.

Current human-evidence status

Human evidence exists in more than one kind, and the kinds should not be mixed. People have endogenous MOTS-c that can be measured in blood or muscle. Exercise can be associated with changes in those measurements. Observational cohorts treat the peptide as a biomarker.^4,3

The inventory is in what evidence actually exists in humans.

Phase 2a status

NCT07505745 exists. It is Phase 2a, randomized, double-blind, and placebo-controlled. The status reviewed on 1 September 2026 is Recruiting. No results are posted. The existence of the registry does not establish a metabolic benefit.⁵

FDA approval status

MOTS-c is not an FDA-approved drug. In July 2026, an advisory committee evaluated MOTS-c-related bulk substances for compounding. That meeting is not approval, not final inclusion on the 503A list, and not Mexican law.^7,6

Under the 2026 WADA framework, MOTS-c appears as a metabolic modulator. That anti-doping status is also not a medical approval.⁹

A lot certificate documents identity and purity. See the certificate archive. It does not show that the peptide improves metabolism in people.