MOTS-c: Scientific Profile
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MOTS-c (CAS 1627580-64-6), a 16-amino-acid mitochondria-derived peptide (MDP) encoded in mitochondrial DNA (12S ribosomal RNA region). An AMPK activator and exercise mimetic for research.
MOTS-c (English name MOTS-c, for Mitochondrial ORF of the Twelve S rRNA type-c) is a naturally occurring 16-amino-acid peptide belonging to the family of mitochondrial-derived peptides (MDP). Its particularity is that it is not encoded in nuclear DNA like most peptides but in the mitochondrial genome, within the 12S ribosomal RNA region, which places it at the center of communication between the mitochondrion and the rest of the cell.
From a functional standpoint, MOTS-c behaves as a metabolic regulator. Under conditions of metabolic stress it has been described as able to translocate to the cell nucleus, where it participates in the regulation of adaptive-response gene expression, an unusual behavior for a peptide of mitochondrial origin that has attracted great interest in research.
The studied mechanism of action of MOTS-c centers on the AMPK pathway (AMP-activated protein kinase), a key energy sensor of the cell. In preclinical models, activation of this pathway is associated with effects on glucose metabolism, energy homeostasis, and insulin sensitivity. For this reason, MOTS-c has been studied as a tool in models of metabolism, exercise, and aging, where an age-associated decline in its levels has been documented.
In research, MOTS-c is used as a tool for studying mitochondria-nucleus signaling, the AMPK pathway, glucose homeostasis, the response to exercise, and models of metabolic aging.
MOTS-c is supplied as a lyophilized powder for reconstitution. Frozen storage protected from light is recommended, along with reconstitution using the sterile diluent indicated in the protocol. This product is offered exclusively as a research reagent (research use only): it is not intended for the diagnosis, prevention or treatment of any disease, nor for human or veterinary consumption.
Mechanism of action
MOTS-c acts primarily as a systemic metabolic regulator:
AMPK activation:
- Inhibe el ciclo de la metionina-folato
- Aumenta ratio AMP/ATP intracelular
- Activa AMPK en músculo esquelético
- Promotes insulin-independent glucose uptake
Glucose metabolism:
- Increases GLUT4 expression
- Improves hepatic insulin sensitivity
- Reduces gluconeogenesis
- Normalizes blood glucose in diabetic models
Lipid metabolism:
- Increases β-oxidation of fatty acids
- Reduces hepatic fat accumulation
- Improves lipid profile
- Promotes "browning" of white fat
Mitochondrial function:
- Promotes mitochondrial biogenesis
- Improves oxidative capacity
- Reduces oxidative stress
Mechanism summary
Peptide derived from the mitochondrial genome that activates AMPK; it enhances insulin-independent muscle glucose uptake (GLUT4), improves insulin sensitivity and the β-oxidation of fatty acids, and induces nuclear translocation that modulates the expression of mitochondrial genes.
Clinical Studies (8)
- MOTS-c is an exercise-induced mitochondrial-encoded regulator (Lee C, et al. · Nature Communications · 2021) — Discovery of MOTS-c as an exercise-induced mitochondrial regulator. PMID 33473109.
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (Lee, et al. · Cell Metabolism · 2015) PMID 25738459.
- MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism (Lee, et al. · Free Radical Biology & Medicine · 2016) PMID 27216708.
- Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization. (Elhusseiny R, et al. · Med Sci Sports Exerc · 2025) PMID 40674654.
- Circulating levels of MOTS-c in patients with breast cancer treated with metformin. (Cuyàs E, et al. · Aging (Albany NY) · 2022) PMID 36490309.
- Effect of aerobic and resistance exercise on the mitochondrial peptide MOTS-c in Hispanic and Non-Hispanic White breast cancer survivors. (Dieli-Conwright CM, et al. · Sci Rep · 2021) PMID 34413391.
- MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. (Zheng Y, et al. · Front Endocrinol (Lausanne) · 2023) PMID 36761202.
- The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis. (Zhou Q, et al. · Diabetol Metab Syndr · 2024) PMID 39160573.
Warnings
MOTS-c is a compound exclusively for research use (RUO); the following warnings and handling considerations apply to its use in the laboratory:
- Research compound
- Hypoglycemia
- Severe kidney disease
- Pregnancy
Technical data
- CAS
- 1627580-64-6
- Molecular formula
- C101H152N28O22S2
- Molecular weight
- 2174.63 Da
- Compound type
- peptide
- Storage
- -20 °C liofilizado; 2-8 °C reconstituido
- Shelf life (lyophilized)
- 24 months
- Shelf life (reconstituted)
- 21 days refrigerated
- Light-sensitive
- Sí
Available for research
MOTS-c is available as a research-use-only (RUO) reagent with HPLC-verified purity and a per-batch COA:
Frequently asked questions about MOTS-c
What is MOTS-c?
MOTS-c (CAS 1627580-64-6), a 16-amino-acid mitochondria-derived peptide (MDP) encoded in mitochondrial DNA (12S ribosomal RNA region). An AMPK activator and exercise mimetic for research.
What is the mechanism of action of MOTS-c?
Peptide derived from the mitochondrial genome that activates AMPK; it enhances insulin-independent muscle glucose uptake (GLUT4), improves insulin sensitivity and the β-oxidation of fatty acids, and induces nuclear translocation that modulates the expression of mitochondrial genes.
What is MOTS-c investigated for?
In preclinical research, MOTS-c is studied mainly in: AMPK activation; Insulin sensitivity; Fatty acid β-oxidation. Material for scientific research use only.
What are the chemical properties of MOTS-c?
Molecular formula C101H152N28O22S2; molecular weight 2174.63 Da; CAS number 1627580-64-6.
How is MOTS-c stored?
Condiciones de conservación: -20 °C liofilizado; 2-8 °C reconstituido; estabilidad liofilizado: 24 meses; una vez reconstituido: 21 días refrigerado; protéjase de la luz.
What routes of administration are studied for MOTS-c?
In the research models the following are described: Subcutaneous. Use is exclusively for scientific research.