MOTS-c — Mitochondria-Encoded Metabolic Regulatory Research Peptide | Klene Peptides

For Research Use Only | Not for Human or Veterinary Administration

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide of extraordinary biological significance: it is encoded not by the nuclear genome, but by the mitochondrial 12S rRNA gene — placing it among a small family of mitochondria-derived peptides (MDPs) that function as systemic hormones. First characterized by Lee et al. in 2015 in Cell Metabolism, MOTS-c regulates metabolic homeostasis by activating the AMPK pathway, modulating the folate-methionine cycle, and driving retrograde mitochondria-to-nucleus signaling that reshapes nuclear gene expression in response to metabolic status. Its demonstrated capacity to independently increase skeletal muscle glucose uptake and reduce adiposity in preclinical models — mimicking the metabolic adaptations of aerobic exercise — has positioned it as one of the most compelling compounds in metabolic aging, insulin resistance, and longevity research. Klene Peptides supplies MOTS-c to USA research institutions with verified purity and same-day fulfillment.

Every vial from Klene Peptides includes:

Chemical Identity & Structural Profile

Parameter	Value
Full Name	MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c)
Sequence (1-letter)	MRWQEMGYIFYPRKLR
Amino Acid Count	16
Molecular Weight	~2,174 Da
CAS Number	1627580-50-8
Genomic Origin	Mitochondrial 12S rRNA gene; small ribosomal subunit open reading frame
Classification	Mitochondria-Derived Peptide (MDP) / Mitokine
Appearance	White lyophilized powder
Solubility	Water, PBS, 0.9% saline
Storage	Lyophilized: −20°C; Reconstituted: 4°C, use within 21 days

MOTS-c belongs to a class of bioactive peptides encoded within mitochondrial ribosomal RNA reading frames — a discovery that fundamentally expanded understanding of the mitochondrial genome’s regulatory capacity beyond its established role in encoding respiratory chain subunits. The peptide functions as a hormone-like signal, translocating from mitochondria to the cytoplasm and nucleus in response to metabolic stress.

Mechanism of Action

Primary Signaling Pathways

Pathway	Mechanism	Research Implication
AMPK Activation	MOTS-c disrupts folate-methionine cycle → AICAR accumulation → AMPK phosphorylation	Central energy sensor activation; glucose uptake stimulation
Folate-Methionine Cycle Modulation	MTHFD1L inhibition → methylene-THF accumulation → AICAR	Metabolic stress signal integration
GLUT4-Mediated Glucose Uptake	AMPK → GLUT4 translocation to plasma membrane	Insulin-independent skeletal muscle glucose utilization
Mitochondrial Biogenesis	AMPK → PGC-1α activation	Mitochondrial number and efficiency improvement
FOXO1 Suppression	Anti-gluconeogenic hepatic signaling	Hepatic glucose output reduction
Adipogenesis Inhibition	Lipogenic gene expression suppression	Adipose reduction mechanistic research
Nuclear Gene Regulation	Retrograde mitochondria-to-nucleus communication	Transcriptional adaptation to metabolic state

Exercise Mimetic Properties

Parameter	MOTS-c Effect	Physiological Parallel
AMPK activation	Comparable to acute aerobic exercise	Exercise-like metabolic signal
Skeletal muscle glucose uptake	Significant increase (GLUT4-dependent)	Mimics insulin + contraction-mediated uptake
Adipose reduction	Reduction in high-fat diet models	Comparable to caloric restriction adaptations
Mitochondrial function	Improved respiratory efficiency	Endurance-training-like mitochondrial adaptation

Pharmacokinetic & ADME Profile

Parameter	Value	Notes
Molecular Weight	~2,174 Da	Moderate size; SC preferred
Primary Route (Research)	SC, IP	Systemic metabolic effects demonstrated
Bioavailability (SC)	High (estimated)	Demonstrated systemic metabolic activity
Plasma Half-Life	~30–60 minutes (preliminary data)	Short; metabolic effects outlast PK window
Distribution	Systemic — skeletal muscle, liver, adipose	Key metabolic target tissues
Cellular Uptake	Cell-penetrating properties	Enters cells independent of receptor-mediated endocytosis
Endogenous Regulation	Exercise-induced elevation	Serum MOTS-c increases with physical activity
Age Dependence	Declines with age	Parallels age-associated metabolic decline
Metabolism	Proteolytic	Standard peptide degradation
Excretion	Renal	Metabolite clearance

Research Applications

Metabolic Syndrome & Insulin Resistance

Research Model	Observed MOTS-c Effect
High-fat diet murine model	Reduced weight gain; improved insulin sensitivity
Db/db diabetic mice	Improved glucose tolerance; reduced fasting glucose
Skeletal muscle insulin resistance	Restored GLUT4-mediated glucose uptake
Hepatic glucose production	Reduced gluconeogenesis via FOXO1 suppression

Key reference: Lee C, et al., Cell Metabolism 2015

Aging & Longevity Research

Parameter	Research Finding
Plasma MOTS-c levels	Decline with age; lower in elderly and diabetic populations
Mitochondrial aging	MOTS-c rescues age-related mitochondrial dysfunction markers
Frailty and sarcopenia	Muscle mass and physical function preservation in aged models
Longevity metrics	Improved healthspan correlates in model organisms

Exercise Physiology

MOTS-c serum levels increase acutely with aerobic exercise in human subjects
Single administration mimics multiple endurance training adaptations
Skeletal muscle fiber type modulation under active investigation
Physical capacity decline in aging populations as a research application

Obesity & Adipose Tissue Research

Research Dosing Reference

For scientific reference only — not prescriptive recommendations

Research Model	Reported Dose Range	Route	Duration
Metabolic syndrome (rodent)	5–15 mg/kg/day	IP, SC	4–8 weeks
Insulin resistance models	5–10 mg/kg	IP	Acute or repeated dosing
Aging / longevity models	5 mg/kg 3× per week	SC	4–12 weeks
In vitro assays	1–100 nM	Cell culture media	Per experimen

Ranges derived from Lee et al., Cell Metabolism 2015; Reynolds et al., Nature Aging 2021.

Reconstitution Reference

Lyophilized Amount	Bacteriostatic Water	Concentration
5 mg	2.5 mL	2.0 mg/mL
10 mg	5.0 mL	2.0 mg/mL

Klene Peptides Quality Standards

Certificate of Analysis — Standard Parameters

Every batch supplied by Klene Peptides is verified against the following analytical benchmarks:

Test	Specification	Method
Purity	≥99%	HPLC (High-Performance Liquid Chromatography)
Molecular Identification	Confirmed	HPLC-MS (High-Performance Liquid Chromatography – Mass Spectrometry)
Water Content	<1.5%	—

What Every Klene Peptides Order Includes

Ordering MOTS-c for Your Research Program

Important Research Compliance Notice

All products sold by Klene Peptides are strictly for in vitro research and laboratory investigation purposes only. MOTS-c supplied by KlenePeptides.net has not been evaluated by the FDA for human safety or efficacy. It is not approved for human or veterinary administration. Purchase, possession, and use must comply with all applicable federal, state, and local regulations. This content is intended for licensed researchers and qualified scientific personnel only.

Scientific References

Lee C, et al. "The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance." Cell Metabolism. 2015;21(3):443-454.
Reynolds JC, et al. "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis." Nature Aging. 2021;1:181-183.
Kim SJ, et al. "The mitochondrial-derived peptide MOTS-c: a new principle in mitochondrial medicine." Ageing Res Rev. 2021;72:101482.
Cobb LJ, et al. "Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers." Aging (Albany NY). 2016;8(4):796-809.
Lu H, et al. "MOTS-c improves insulin sensitivity in adipocytes from type 2 diabetic patients." J Diabetes Res. 2019.
Ming W, et al. "MOTS-c: a mitochondria-derived peptide regulating cellular and organismal homeostasis." Mol Aspects Med. 2022.
PubChem. MOTS-c peptide reference. https://pubchem.ncbi.nlm.nih.gov