16-amino-acid mitochondria-encoded peptide. Studied for folate-cycle inhibition, AICAR accumulation, AMPK activation, and exercise-induced metabolic homeostasis signalling — a unique retrograde mitochondrial-to-nuclear messenger.
MOTS-c (Mitochondrial Open Reading frame of the Twelve S rRNA type-c) is unique among peptides: it is encoded within the mitochondrial genome itself, not the nuclear genome. Discovered in 2015 by the Cohen lab, MOTS-c functions as a retrograde signalling molecule that communicates mitochondrial functional status to nuclear gene expression.
MOTS-c is synthesised in mitochondria and translocates to the cytoplasm under metabolic stress. Nuclear translocation also occurs, enabling direct gene-expression modulation.
MOTS-c targets methylenetetrahydrofolate dehydrogenase (MTHFD2) in the one-carbon folate pathway. Inhibition causes accumulation of AICAR, which mimics AMP and binds the AMPK γ-subunit.
AMPK phosphorylation cascades upregulate PGC-1α, NRF1/NRF2, and TFAM — transcription factors driving mitochondrial biogenesis and oxidative metabolism gene programmes.
In diet-induced obesity mouse models, exogenous MOTS-c administration restored insulin sensitivity, reduced fasting glucose, and decreased intra-hepatic lipid accumulation. Effects correlated with AMPK phosphorylation status in skeletal muscle and liver biopsy specimens.
Refs: Lee C et al., Cell Metab (2015); Reynolds JC et al., Nat Commun (2021)
Circulating MOTS-c is upregulated by acute exercise and declines with age. Studies show MOTS-c administration in aged mice partially restored exercise capacity and skeletal-muscle oxidative phenotype, suggesting a role in age-related mitochondrial dysfunction.
Refs: Reynolds JC et al., Nat Commun (2021); Yang Y et al., Aging Cell (2020)
Each batch is independently tested by a third-party ISO-accredited laboratory. The analysis below reflects Batch AV-2025-MOT-031, tested 28 January 2025.
| Test Parameter | Method | Specification | Result | Status |
|---|---|---|---|---|
| Identity (sequence) | ESI-MS / MS-MS | Matches theoretical m/z | Confirmed (2174 Da) | PASS |
| Purity (HPLC) | RP-HPLC C18, 210nm | ≥98.0% | 99.2% | PASS |
| Water content | Karl Fischer | ≤8.0% | 5.9% | PASS |
| Heavy metals | ICP-MS | ≤10 ppm | <2 ppm | PASS |
| Bacterial endotoxins | LAL chromogenic | ≤10 EU/mg | <1 EU/mg | PASS |
| Form | Temperature | Duration |
|---|---|---|
| Lyophilised powder | −20°C (strongly preferred) | 24 months |
| Reconstituted (BAC water) | 2–8°C | ≤21 days |
| Reconstituted (saline) | 2–8°C | ≤5 days |
Wipe vial with 70% IPA, allow to dry. MOTS-c is structurally fragile — handle with care.
For 10 mg vial, add 2 mL BAC water → 5 mg/mL stock. Inject very slowly along the inner wall to avoid mechanical stress.
Swirl gently — never vortex or shake. Aggressive agitation can fragment the 16-AA chain.
Store strictly at 2–8°C; minimise freeze-thaw cycles. Aliquot if multiple uses planned.
MOTS-c is encoded directly within mitochondrial DNA — a discovery that reshaped understanding of the mitochondrial genome. It belongs to a small class called "mitochondrial-derived peptides" (MDPs) which also includes humanin and the SHLP family. This origin allows MOTS-c to function as a real-time messenger of mitochondrial functional status to nuclear gene-expression programmes.
Circulating MOTS-c is significantly upregulated by acute exercise in humans and rodents. Research suggests it may function as an exercise-mimetic, mediating some metabolic adaptations to physical activity. Many preclinical protocols administer MOTS-c shortly before exercise to study amplification of acute exercise responses.
Published research protocols favour pulsing regimens — typically 5–10 mg administered 2–3 times weekly — to mimic physiological MOTS-c release patterns rather than producing sustained plasma elevation. This approach aligns with the peptide's role as an acute metabolic signal rather than a chronic effector.
Yes, indirectly. AMPK activation downstream of MOTS-c upregulates PGC-1α, the master regulator of mitochondrial biogenesis. Studies in skeletal muscle demonstrate increased mtDNA copy number, complex I-IV protein expression, and oxygen-consumption rate following sustained MOTS-c administration in rodent models.
Independently verified by third-party ISO-accredited laboratory. COA available on request.
View MOTS-c in Store → Reconstitution Protocol Guide