MOTS-C

At a glance

Strengths

10 mg and 40 mg

Also known as

Mitochondrial open reading frame of the 12S rRNA type-c; MOTS-c (human)

CAS number

1627580-64-6

Molecular formula

C101H152N28O22S2

Molecular weight

2174.6 g/mol

Sequence

Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR)

PubChem CID

146675088

What MOTS-c is

MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c ¹. It belongs to the mitochondrial-derived peptides, small peptides encoded by short open reading frames in mitochondrial DNA. A 2020 review counted eight of them: MOTS-c, encoded in the 12S rRNA gene (MT-RNR1), and humanin with six small humanin-like peptides, encoded in the 16S rRNA gene ². In 2018 a University of Southern California laboratory reported that MOTS-c moves into the nucleus during metabolic stress such as glucose restriction, in an AMPK-dependent way. There it was reported to regulate genes with antioxidant response elements and to interact with the transcription factor NRF2 ³. A 2019 review from the same group describes MOTS-c as a mitochondrial-encoded factor that regulates nuclear gene expression ⁴.

Sequence and chemical identity

The human sequence is Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg. PubChem (CID 146675088) gives C101H152N28O22S2 and 2174.6 g/mol. The two sulfur atoms belong to the methionines at positions 1 and 6, and a tryptophan sits at position 3. Three arginines and one lysine give the peptide a strong positive charge. PubChem's synonyms include a trifluoroacetate salt, one of the forms in which synthetic MOTS-c has been catalogued. A 2019 anti-doping assay tracked animal MOTS-c analogues alongside human MOTS-c ¹, so the species of origin matters for identity testing.

Regulatory status

There is no FDA-approved MOTS-c product, and a Drugs@FDA search finds no match. After MOTS-c was nominated for pharmacy compounding, FDA assigned it to category 2, the group with potential significant safety risks, and the nominations were later withdrawn. FDA's summary mentions possible immunogenicity and difficulties with peptide-related impurities and characterization of the substance. It adds that FDA has not identified any human exposure data for drug products containing MOTS-c (FDA page last updated April 22, 2026). MOTS-c also appeared on the agenda for the July 23, 2026 meeting of FDA's Pharmacy Compounding Advisory Committee. As of October 3, 2026, FDA had published neither minutes nor a decision from that meeting. The MOTS-c on this page is a laboratory reagent, not a medicine.

Published research

The literature has three main parts: cell and rodent studies with synthetic peptide, measurements of the body's own MOTS-c in people, and analytical method work. Rodent papers on MOTS-c are mostly written up as effects in particular models; those are left out here. A 2020 review of mitochondrial-derived peptides reported that, in humans, muscle expression of these peptides rises in response to stresses that perturb mitochondria, such as exercise ². On the analytical side, the 2019 anti-doping laboratory developed a liquid chromatography and mass spectrometry (LC/MS) test for MOTS-c in human plasma. The method was validated to World Anti-Doping Agency laboratory standards. It also covers four metabolites formed in vitro and two oxidation products of the peptide ¹.

What is not known

No controlled trial of synthetic MOTS-c in people appears in PubMed as of October 2026, and FDA has found no human exposure data. Measurements of the body's own MOTS-c are also uncertain. When the 2019 LC/MS method was compared with a commercial ELISA, the two gave considerably different MOTS-c levels ¹. Results from immunoassays and from mass spectrometry therefore cannot be assumed to agree. Three of the five papers cited here, the 2020 and 2019 reviews and the 2018 study, come from authors at one laboratory, and in each the senior author disclosed a consulting role and shareholding in CohBar, Inc. ^{2 3 4}.

Laboratory storage and handling

Store MOTS-c as stated on its certificate of analysis and product label. The solid-state literature lists oxidation, deamidation and aggregation among the slow reactions of dry peptides, with temperature and moisture as major influences ⁵. Oxidation is directly relevant here. The 2019 LC/MS assay included two oxidation products of MOTS-c among the species it tracks ¹, and the sequence carries two methionines and a tryptophan. Keeping the container closed until use limits exposure to air and humidity.

Quality testing

Useful checks on a MOTS-c certificate of analysis:

• Identity: mass spectrometry matching 2174.6 g/mol, with any +16 Da peaks noted, since each corresponds to one added oxygen atom.
• Purity: reverse-phase HPLC, with oxidation products reported as related impurities ¹.
• Species: confirmation that the material is the human sequence, not an animal analogue ¹.
• Salt and content: the counter-ion and the net peptide content.

The purity of a given lot is stated on that lot's certificate.