MOTS-C

MOTS-c research peptide in Thailand

MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded inside the mitochondrial 12S rRNA gene, studied in preclinical models of AMPK activation, insulin sensitivity, metabolic homeostasis, and exercise- and age-related decline. It was first characterised by Changhan David Lee and Pinchas Cohen at USC, and it is one of the reference tools for research into how mitochondria signal back to the nucleus.

This listing is for laboratory research use only. The MOTS-c evidence base is almost entirely preclinical — cell culture and mouse models — with no established human protocols; it is not a medicine, supplement, or metabolic product.

Quick facts

Product

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c)

CAS

1627580-64-6

Molecular weight

~2.17 kDa

Origin

Encoded in mitochondrial DNA, not the nuclear genome

Form

Lyophilised powder, sealed vial

Intended use

laboratory research use only

How MOTS-c works

Unlike almost every other peptide in a research catalogue, MOTS-c is not transcribed from the nuclear genome — it is read out of an open reading frame hidden inside the mitochondrial 12S rRNA gene. Under metabolic stress it moves out of the mitochondrion into the cytoplasm, where the published mechanism runs through the folate–methionine one-carbon cycle: MOTS-c inhibits the enzyme MTHFD2, purine biosynthesis slows, the intermediate AICAR accumulates, and rising AICAR switches on AMPK — the same energy-sensing kinase engaged by aerobic exercise and by metformin.

A second arm of the mechanism is transcriptional. Kim and colleagues showed that under glucose restriction and oxidative stress MOTS-c translocates further, into the nucleus, where it associates with antioxidant response elements and works with NRF2 to drive stress-defence and metabolic genes. That combination — a mitochondrially encoded peptide directly regulating nuclear transcription — is why the literature describes MOTS-c as a retrograde signal rather than a conventional hormone. These are findings of specific published studies, not outcomes attributed to this product.

Key research findings

• In mice, MOTS-c targeted skeletal muscle and inhibited the folate cycle to activate AMPK; treatment prevented age-dependent and high-fat-diet-induced insulin resistance as well as diet-induced obesity (Lee, Cell Metabolism, 2015).
• Under metabolic stress, MOTS-c translocated from the mitochondria to the nucleus, bound antioxidant response elements, and upregulated stress-response genes including HO-1 and NQO1 via NRF2 in an AMPK-dependent manner (Kim, Cell Metabolism, 2018).
• Exercise induced endogenous MOTS-c expression in human skeletal muscle and circulation, and treatment improved treadmill performance in young, middle-aged, and older mice, including when started late in life (Reynolds, Nature Communications, 2021).

Research applications

• AMPK activation and cellular energy-sensing pathway studies
• Insulin sensitivity, glucose uptake, and diet-induced obesity models
• Mitochondrial retrograde signalling and mitochondria-to-nucleus communication
• Exercise-mimetic pharmacology, benchmarked against AICAR and other AMPK activators
• Ageing, healthspan, and skeletal-muscle homeostasis research
• Folate–methionine and one-carbon metabolism investigation

Dosing in the literature

No human protocols are established for MOTS-c, so the figure above is a reference-scale estimate rather than a trial-derived range. Published rodent work used roughly 5 mg/kg/day for short glucose-tolerance experiments and 0.5 mg/kg/day over eight weeks for chronic obesity models (Lee, Cell Metabolism, 2015), with 5–15 mg/kg daily or intermittent regimens in the ageing and exercise work (Reynolds, Nature Communications, 2021). This is a summary of parameters as reported in research references, not administration guidance. To model concentrations for a defined protocol, use the MOTS-c peptide calculator.

Reconstitution & storage

Solvent

Bacteriostatic water — standard for lyophilised research peptides

Mixing

Add solvent down the vial wall and swirl gently until dissolved; do not shake

Storage

Refrigerated (2–8 °C) after reconstitution, in common laboratory practice

Use within

About four weeks once reconstituted

Freeze / light

Keep lyophilised powder frozen or cold, sealed, and protected from light

These are common laboratory handling conventions, not preparation instructions. In Thailand's heat and humidity, the practical risk is ambient exposure — minimise time out of cold storage during handling and courier transit, and keep vials out of direct sunlight.

Selected research

• The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance — Cell Metabolism, 2015
• The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress — Cell Metabolism, 2018
• MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis — Nature Communications, 2021
• MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases — Int J Mol Sci, 2022 (review)
• Browse all indexed MOTS-c literature on PubMed

Related compounds

• NAD+ — the central redox coenzyme and sirtuin substrate; studied alongside MOTS-c wherever mitochondrial energy metabolism and ageing intersect, though through a coenzyme rather than a signalling-peptide mechanism.
• SS-31 — a mitochondria-targeted tetrapeptide studied for its binding to cardiolipin in the inner mitochondrial membrane; a structural counterpart to MOTS-c's transcriptional and AMPK-mediated route.
• Bacteriostatic water — the standard diluent used to reconstitute lyophilised research peptides.

See also: mitochondrial research compounds and more mitochondrial and cellular research compounds.

MOTS-c FAQ

Compliance note

MOTS-c is supplied for laboratory research use only. It is not for human or veterinary use, and it is not intended to diagnose, treat, cure, or prevent any disease. All findings referenced above are the results of specific published studies, not claims about this product.