What is MOTS-c?

MOTS-c is a mitochondrial-derived peptide: a 16-amino-acid chain read from a short open reading frame inside the mitochondrial 12S rRNA gene. The name spells out that origin: mitochondrial open reading frame of the 12S rRNA type-c. ^[1]

Changhan Lee, Pinchas Cohen and colleagues at the University of Southern California reported it in Cell Metabolism in March 2015. They went looking because an earlier signalling peptide, humanin, had already been traced to a short open reading frame in mitochondrial DNA. ^[1] Researchers now group the two as mitochondrial-derived peptides. ^[11]

The body makes MOTS-c on its own, and it circulates in blood. Laboratories also make it by peptide synthesis. MOTS-c in 10mg vials is in stock with a batch certificate.

In the published models, MOTS-c works mainly through AMPK, the enzyme cells use to sense energy. The 2015 paper reported that MOTS-c acts on folate metabolism and the purine synthesis tied to it, which leads to AMPK activation. It named skeletal muscle as the apparent main target organ. ^[1] A 2023 review calls this route the Folate-AICAR-AMPK pathway. ^[12]

Three later findings add to that picture.

In 2018 the same group reported that MOTS-c moves into the nucleus under metabolic stress, in an AMPK-dependent way. There it regulated genes with antioxidant response elements and interacted with the transcription factor NRF2. ^[4]

In 2024 a study reported that MOTS-c binds casein kinase 2 (CK2) directly and activates it in cell-free systems. In mice it raised CK2 activity in muscle and lowered it in fat. ^[5]

The third finding is genetic. An East Asian mitochondrial DNA variant, m.1382A>C, swaps lysine for glutamine at position 14 of MOTS-c (K14Q). The K14Q form bound CK2 less and did not activate it. ^[5] A meta-analysis of three cohorts with 27,527 people linked the variant to a higher prevalence of type 2 diabetes in men and found no such link in women. ^[13]

Every step here comes from cell work, mouse work or genetic association. None of it measures what synthetic MOTS-c does in a person.

MOTS-c is a linear 16-residue peptide with a free amine at the start, a free carboxylic acid at the end and no other modifications. PubChem writes it as H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH. ^[3]

The identifiers come from PubChem ^[3] and the gene origin from the 2015 paper. ^[1] We checked each value on 29 September 2026.

Four details in the sequence matter in the lab. Methionine sits at positions 1 and 6, and tryptophan at position 3. Arginine appears three times and lysine once, so the peptide carries a strong positive charge. Position 14 is the lysine that the K14Q variant replaces.

Methionine is the residue to watch. The anti-doping test built for MOTS-c tracks two oxidation products of the peptide. ^[8] Methionine oxidation shows up on mass spectrometry as a gain of 16 Da. ^[14] An oxidised molecule looks identical in the vial, and only the mass spectrum shows it.

MOTS-c research has examined metabolism, exercise capacity, ageing, bone, infection and heart injury, nearly all of it in cells and rodents. A PubMed search on 29 September 2026 returned 257 records with MOTS-c in the title or abstract. ^[15] The human records measure the MOTS-c people make themselves. We found no published controlled trial that gave MOTS-c to people.

Each finding describes what one study reported in its own model. The mouse and rat results describe the biology researchers are testing, and none of them is a claim about a research vial or about people.

The MOTS-c evidence is broad in animal models and thin everywhere else. Five limits stand out.

1. No controlled trial of MOTS-c in people. The one registered human trial in this family tested CB4211, an analogue developed by CohBar. It was a randomised, double-blind, placebo-controlled phase 1 study with 88 participants, completed on 19 April 2021, and the registry shows no posted results. ^[9] The Alzheimer's Drug Discovery Foundation reports that CB4211's development stopped when CohBar dissolved, and that no trials of MOTS-c or its analogues are running. ^[22]
2. Human levels are unsettled. The immunoassay studies in the table report values around 0.5 ng/mL in one lab and around 470 to 560 ng/mL in another. ^[6][7] In 2019 an anti-doping group built a mass spectrometry test validated to WADA's laboratory standard. It could not confirm the 45.9 to 218.5 ng/mL that a commercial immunoassay reported for 20 healthy people. ^[8] Every human link to age, obesity or diabetes rests on those immunoassays.
3. One research network wrote the core papers. The discovery, nuclear, exercise and CK2 papers come from the University of Southern California group. Their authors declare consulting roles or shares in CohBar. ^[4][20] The 2024 paper states that UCLA licensed the MOTS-c intellectual property to CohBar, with Pinchas Cohen named as an inventor. ^[5]
4. Pharmacokinetics are unknown. The foundation's report lists the half-life as not available, and states that the half-life of MOTS-c given to people has not been established. ^[22] In a 2023 mouse colitis study, MOTS-c given by mouth produced no significant improvement. A modified analogue showed a longer half-life than MOTS-c in vitro. ^[23]
5. One paper has been retracted. A 2019 fracture study was withdrawn in 2021 over inaccuracies in its images. ^[24]

A careful reader can take the mechanism work seriously and still see that the human question is open.

No published study reports adverse events from giving MOTS-c to people, because no such study has been published. We searched PubMed for MOTS-c with adverse, safety, toxicity and trial terms. The human records measured natural MOTS-c levels only. The rodent and cell studies that gave MOTS-c report outcomes, and their abstracts record no adverse events.

Two secondary records exist, and both carry limits.

• The CB4211 analogue trial. The Alzheimer's Drug Discovery Foundation, citing CohBar press releases, reports that the phase 1a study was paused in 2018 over persistent mild skin reactions at the delivery site, described as painless bumps. The study resumed and finished. CohBar's topline results reported no serious adverse events, and full safety data were never disclosed. ^[22]
• Unverified self-reports. USADA states that people who say they bought MOTS-c online report increased heart rate or palpitations, local or generalised immune reactions, insomnia and fever. USADA adds that no data exist on long-term use. ^[25]

Neither record is a controlled study of MOTS-c. Both are reported here as the published record.

MOTS-c is not named in the Poisons Standard. We searched the full text of the June 2026 instrument (F2026L00633), which commenced on 1 June 2026, and found no entry for MOTS-c. ^[10] A missing entry is a separate question from approval. USADA states that MOTS-c is not approved by the US FDA for use in humans. ^[25] Our guide to Australian peptide law and the Poisons Standard explains how the schedules work and how unapproved goods are treated.

For sport, the position is plain. The WADA 2026 Prohibited List names MOTS-c under S4.4.1, activators of AMPK, and prohibits it at all times, in and out of competition. Substances in S4.4 are non-Specified Substances. The List took effect on 1 January 2026. ^[2]

Sport Integrity Australia names MOTS-C among its common examples of peptides prohibited in sport. It warns that possession or use can lead to an anti-doping rule violation and a ban. ^[26] USADA considers a Therapeutic Use Exemption highly unlikely, because MOTS-c has no approved therapeutic use. ^[25] Testing labs have had a validated plasma method for MOTS-c since 2019. ^[8]

MOTS-c and NAD+ both come up in mitochondrial research, and they are different kinds of molecule. MOTS-c is a 16-amino-acid peptide. NAD+ is a dinucleotide coenzyme with no amino acids.

The MOTS-c column is drawn from the sources above. ^[3][2] The NAD+ column comes from the same PubChem, Poisons Standard and WADA checks we ran for every compound on 29 September 2026. Our NAD+ explainer covers that coenzyme in full. MOTS-c sits in our metabolic research peptides range.

No published stability study covers lyophilised research MOTS-c, so general peptide guidance applies. NIBSC advises keeping peptides dry, cool and dark, at 4°C or colder, with -20°C preferred for long-term storage. ^[27] Sigma-Aldrich notes that sequences containing C, M or W are prone to air oxidation, and advises against repeated freezing and thawing of powders and solutions. ^[28]

MOTS-c carries two of those flagged residues: methionine twice and tryptophan once. Keep sealed vials cold, dark and capped tight. Aliquot a solution so each portion thaws once.

For solvent, the published cell work dissolved MOTS-c in phosphate-buffered saline, which served as the vehicle control. ^[29] We stock BAC Water, sterile water with 0.9% benzyl alcohol, in 3ml vials at A$8 for laboratory reconstitution. Our guide to reconstituting peptides covers solvent choice and the mg per mL maths. The peptide storage guide covers temperatures, light and freeze-thaw for powders and solutions.

Peptides Collective sells MOTS-c for laboratory research use only, in 10mg vials at A$78. Stock ships from Western Australia with tracking.

An independent lab tests every batch before it goes on sale. The certificate reports purity by HPLC and identity by mass spectrometry, and it is published under the batch number printed on the vial. Search the certificate of analysis library by that number to match the report to the vial in your hand.

Read the certificate against the structure table above. The identity result should correspond to a peptide of 2174.6 g/mol, and a peak 16 Da heavier points to oxidised methionine. Our guide on how to read a peptide certificate of analysis explains the HPLC trace and the mass spectrum. The MOTS-c product page links the certificate for the current batch.

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, studied since 2015 mostly in cells and mice, where it acts through AMPK and CK2. The human record measures natural levels with assays that disagree, and no controlled trial of MOTS-c itself has been published. In Australia it has no Poisons Standard entry, and WADA prohibits it at all times. For a research vial, the batch certificate is the evidence that settles what is inside.