MOTS-c
10 MGMOTS-c (MOTSc) — mitochondrial peptide for research on AMPK and metabolism
Studied therapeutic interests:
MOTS-c — also spelled MOTSc, MOTS-C or Mitochondrial Open Reading frame of the Twelve S rRNA type-c — is an endogenous regulatory peptide of 16 amino acids (MRWQEMGYIFYPRKLR) discovered in 2015 by the Pinchas Cohen group at the University of Southern California. It is encoded by an alternative open reading frame (ORF) located within the MT-RNR1 gene of mitochondrial DNA, encoding the 12S ribosomal RNA. This discovery showed that mitochondrial DNA — long considered to encode only 13 respiratory proteins — also produces additional regulatory peptides.
MOTS-c belongs to the emerging family of MDPs (Mitochondrial-Derived Peptides), which also includes humanin and SHLPs. These peptides act as mitochondrial hormones, detectable in human plasma at picomolar concentrations, with concentrations decreasing 70-80% between ages 20 and 70 — making them biomarkers of interest in research on cellular aging.
The main mechanism of action involves direct activation of AMPK (AMP-activated protein kinase), the cellular energy sensor. In L6 myocytes and HepG2 hepatocytes, stimulation by MOTS-c at 1-10 µM concentrations increases AMPKα phosphorylation (Thr172) and acetyl-CoA carboxylase (Ser79) within 15-30 minutes. Under metabolic stress conditions, MOTS-c also migrates from the mitochondrial compartment to the nucleus to interact with transcription factors (notably NRF2).
At OSMOSE Research, MOTS-c is supplied as a lyophilized powder with HPLC purity ≥ 99.2%. Manufactured in Europe under GMP standards, this research peptide is delivered to France, Belgium, Switzerland, Luxembourg and worldwide internationally with insulated packaging.
- Preclinical research on AMPK pathway and metabolic homeostasis
- Studies on insulin resistance in L6/C2C12 myocytes
- Research on cellular senescence in IMR-90 fibroblasts
- Preclinical models of mitochondrial biogenesis
- Studies on regulation of fatty acid oxidation
- Research on mitochondrial nucleus-mitochondria communication
- Preclinical studies on diet-induced obesity
- Research on the aging process and MDPs biomarkers
MOTS-c is a major peptide in research on the biology of aging and mitochondrial metabolism. The foundational work of Lee, Zeng and Cohen (Cell Metabolism 2015) established its role as a metabolic regulator via AMPK. Research topics include: restoration of insulin sensitivity in diet-induced obesity models, MDP interactions with the nucleus (Kim et al. 2018) via interaction with NRF2 and other transcription factors, regulation of the folate pathway, and age-related decline of plasma concentrations. Recent studies (2020-2024) explore the effects of MOTS-c on replicative senescence in IMR-90 fibroblasts, mitochondrial biogenesis, and its role as a biomarker of the aging process.
- HPLC purity ≥ 99.2% verified by RP-HPLC
- Molecular mass certified by ESI-MS
- Endotoxin test < 0.5 EU/mg by LAL method
- Sterility validation
- Sequence verification by MS/MS
Frequently asked questions
Yes. MOTS-c is naturally produced by human mitochondria, unlike most research peptides which are synthetic analogs. It was discovered in 2015 by the P. Cohen group (USC) via bioinformatic analysis of alternative ORFs within mitochondrial DNA.
SPPS synthesis allows obtaining controlled quantities with ≥ 99.2% HPLC purity, incompatible with purification from biological tissues. Synthesis also ensures sequence reproducibility (MRWQEMGYIFYPRKLR) without natural isoforms.
The question remains debated. Current data suggest activation via a mechanism sensitive to the AMP/ATP ratio and folate pathway (inhibition of AICAR transformylase), with an indirect contribution to AMPK activation. This mechanistic question is an active research topic.
The sequence is conserved at over 95% between humans and mice, allowing reasonable translation of murine studies toward human cellular models. The minor differences mainly concern positions 7-9 of the peptide.
Typical concentrations are 1-10 µM in L6 myocytes and HepG2 hepatocytes for AMPK activation. For replicative senescence studies in IMR-90, 100 nM to 1 µM over 48-72h. Physiological plasma concentrations are in the picomolar range, but higher in vitro concentrations are used to observe rapid effects.
Human studies show an 70-80% decrease in plasma concentrations of MOTS-c between ages 20 and 70. In IMR-90 fibroblasts approaching replicative senescence, addition of MOTS-c delays the expression of markers p16^INK4a and SA-β-galactosidase, opening research pathways on MDPs as cellular aging regulators.
Yes. Under metabolic stress conditions, Kim et al. (2018) demonstrated that MOTS-c migrates from mitochondria to the nucleus, where it interacts with NRF2 and other transcription factors to induce expression of oxidative stress response and caloric restriction genes.
Lyophilized MOTS-c dissolves in bacteriostatic water or PBS pH 7.4. Due to its tryptophan (position 3) and methionine (positions 1, 5), avoid prolonged exposure to air and strong oxidizing agents. Stability is 28 days at 4 °C after reconstitution.
Both are MDPs (Mitochondrial-Derived Peptides), but encoded by different ORFs: MOTS-c by MT-RNR1 (12S rRNA), humanin by MT-RNR2 (16S rRNA). Humanin (21-24 amino acids) has primarily neuroprotective effects, while MOTS-c (16 amino acids) has primarily metabolic effects.
Purity ≥ 99.2% HPLC is imperative for quantitative studies on AMPK signaling. Synthesis impurities may include tryptophan oxidation products (position 3), methionine (positions 1, 5), and incorrectly sequenced peptides, which can alter measurements.
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All products on this page are intended exclusively for in vitro scientific research and laboratory use. They are not intended for human or animal consumption, nor for diagnostic or therapeutic use. The buyer assumes full responsibility for compliance with applicable local regulations.