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MOTS-c 10 mg — Peptides Only, research use only
Peptides · Longevity

MOTS-c

Third-party tested · COA with every order
FormulaC101H152N28O22S2MW2174.55

Mitochondrial-derived peptide studied in metabolic homeostasis.

  • Independently tested
  • Lot-matched COA
  • Lyophilized for stability
  • Ships from the USA
Research use only. Not for human or veterinary use. Sold to qualified researchers aged 21+.
$100.002 for $100 — $50 per vial
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MOTS-c$100.002 for $100
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About MOTS-c

Mitochondrial-derived peptide studied in metabolic homeostasis.

Supplied as

10 mg per vial, as a lyophilized powder in a sealed glass vial with a crimped cap. The lot number on the label matches the certificate of analysis in the COA library.

Storage and handling

Store lyophilized powder frozen (−20 °C) or refrigerated, sealed and away from light. Once reconstituted, keep refrigerated (2–8 °C).

Handle in a laboratory setting using appropriate protective equipment. Consult the certificate of analysis and safety data for lot-specific information.

Important research notice. This product is intended solely for in-vitro and laboratory research. It is not a drug, food, supplement or cosmetic, has not been evaluated by the FDA, and must not be used in humans or animals. Peptides Only does not provide usage or dosing information.

Research summary

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded within mitochondrial DNA, in the gene for 12S ribosomal RNA1. It belongs to the small family of mitochondrial-derived peptides and is studied as a signal through which mitochondria may influence metabolism in the rest of the cell and body, with most of the evidence coming from mice and cultured cells1,2.

Also known as
MOTSc · MOTS-c peptide · Mitochondrial open reading frame of the 12S rRNA type-c · Mitochondrial-derived peptide MOTS-c
Sequence
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg

What is MOTS-c?

MOTS-c was described in 2015 by Lee and colleagues, who found a short open reading frame inside the mitochondrial 12S rRNA gene that encodes a 16-residue peptide1. Its sequence is MRWQEMGYIFYPRKLR. Almost all proteins are encoded in the nucleus; MOTS-c is unusual because its code sits in the mitochondrial genome, alongside the related peptides humanin and the small humanin-like peptides (SHLP1 to 6), which are encoded in the 16S rRNA region2.

Peptides Only supplies MOTS-c as a lyophilized powder for laboratory research. Each lot ships with a lot-matched certificate of analysis from an independent lab, with HPLC purity and mass-spec identity, published in the COA library. It is also available in the NAD+ / MOTS-c / SS-31 set.

How MOTS-c is thought to work

In the original study, skeletal muscle appeared to be the main target organ. At the cellular level, MOTS-c inhibited the folate pathway and the de novo purine synthesis linked to it, which led to activation of AMPK, the cell's energy-stress sensor1.

A 2018 follow-up from the same group reported that under metabolic stress, such as glucose restriction, MOTS-c moves into the nucleus in an AMPK-dependent manner and regulates nuclear genes, including genes with antioxidant response elements, while interacting with the transcription factor NRF23. The authors presented this as evidence that the mitochondrial genome encodes factors that can regulate the nuclear genome3.

What the research has examined

Metabolism in mice: in the 2015 study, MOTS-c administration prevented both age-dependent and high-fat-diet-induced insulin resistance in mice, and prevented diet-induced obesity1.

Exercise capacity and aging: Reynolds and colleagues reported that MOTS-c increased physical performance in young, middle-aged and old mice, and that intermittent administration started late in life increased physical capacity in old mice. In the same paper, exercise raised endogenous MOTS-c in human skeletal muscle and in circulation4.

Genetics: an Asian-specific mitochondrial DNA variant, m.1382A>C, changes lysine 14 of MOTS-c to glutamine (K14Q). In a meta-analysis of three cohorts totaling 27,527 people, men carrying the variant had a higher prevalence of type 2 diabetes, and in high-fat-fed male mice the K14Q form did not reproduce the effects of native MOTS-c on weight and glucose tolerance5.

MOTS-c in human studies

Human data so far are observational: researchers measure MOTS-c in blood or muscle rather than administer it. In a study of 10 lean and 10 obese adults, plasma MOTS-c did not differ between groups but correlated with indices of insulin sensitivity, mainly in the lean participants6. In healthy men, circulating MOTS-c was lower with age, while skeletal-muscle MOTS-c expression was about 1.5-fold higher in middle-aged and older men than in young men7. After a single session of endurance exercise, plasma MOTS-c showed only a trend toward an increase, whereas the related peptide humanin rose significantly8.

A 2023 review noted that no effective method of applying MOTS-c in the clinic has been developed9. MOTS-c is not an approved medicine and remains a research compound.

Limitations of the evidence

  • The mechanistic and intervention data come almost entirely from mice and cultured cells1,3,4.
  • Human findings are associations from small cohorts; they do not show what giving MOTS-c would do in people6,7,8.
  • Results do not always line up across models: the antioxidant-gene response seen in cultured cells was not associated with muscle MOTS-c expression in aging men3,7.
  • Several foundational papers come from one research network, and their conflict-of-interest statements disclose that senior authors are consultants to and shareholders of a biotechnology company3,4.

MOTS-c FAQ

Is MOTS-c a peptide or a hormone?

MOTS-c is a 16-amino-acid peptide. Because it is present in plasma and, in mouse studies, acts on tissues such as skeletal muscle, it is often described as a mitochondrial signaling peptide1,9. Whether it behaves as a true circulating hormone in humans has not been established.

What is the difference between MOTS-c and humanin?

Both are mitochondrial-derived peptides, but they come from different mitochondrial genes: MOTS-c from the 12S rRNA region and humanin from the 16S rRNA region2. In one human exercise study, endurance exercise raised circulating humanin significantly, while MOTS-c showed only a trend8.

What is the difference between MOTS-c and SS-31?

MOTS-c is a naturally occurring peptide encoded by mitochondrial DNA that signals to muscle metabolism and the nucleus1,3. SS-31 is a synthetic tetrapeptide designed to bind cardiolipin in the inner mitochondrial membrane10. All three are offered together in the NAD+ / MOTS-c / SS-31 Set.

Is MOTS-c approved by the FDA?

No. MOTS-c is not an approved medicine. It has been studied in cells, in mice and in observational human studies, and a 2023 review noted that no effective clinical application had yet been developed9. Peptides Only sells it for laboratory research only.

How is lyophilized MOTS-c stored?

Keep the lyophilized powder sealed, cold, dry and away from light. Our guide to peptide storage and stability covers the reasons in more detail.

Further reading

References

  1. Lee C, Zeng J, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-54. PubMed 25738459
  2. Kong BS, Lee C, et al. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. Diabetes Metab J. 2023;47(3):315-324. PubMed 36824008
  3. Kim KH, Son JM, et al. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018;28(3):516-524.e7. PubMed 29983246
  4. Reynolds JC, Lai RW, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. PubMed 33473109
  5. Zempo H, Kim SJ, et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY). 2021;13(2):1692-1717. PubMed 33468709
  6. Cataldo LR, Fernández-Verdejo R, et al. Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals. J Investig Med. 2018;66(6):1019-1022. PubMed 29593067
  7. D'Souza RF, Woodhead JST, et al. Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition. Aging (Albany NY). 2020;12(6):5244-5258. PubMed 32182209
  8. von Walden F, Fernandez-Gonzalo R, et al. Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans. J Appl Physiol (1985). 2021;131(3):1035-1042. PubMed 34351816
  9. Zheng Y, Wei Z, et al. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023;14:1120533. PubMed 36761202
  10. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029-50. PubMed 24117165

Research summary reviewed 2026-10-26 against the cited literature.

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