MOTS-c

Volume Pricing

Price per pack (10 vials). Discount applies to this compound only – no mix and match.

MOTS-c — Mitochondrial-Derived Peptide / AMPK-Mediated Metabolic Research

MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a mitochondrial-derived peptide (MDP) encoded not in the nuclear genome but within the 12S rRNA gene of mitochondrial DNA — a discovery that fundamentally expanded the known catalog of mitochondrially encoded peptides when published by Changhan David Lee and colleagues at the University of Southern California in 2015. The 16-amino-acid peptide is produced in mitochondria and, under metabolic stress conditions, translocates to the nucleus where it modulates nuclear gene expression. Its mechanism of action centers on activation of AMPK and the AICAR pathway, positioning MOTS-c as a mitochondrial signal that communicates energy status to the rest of the cell. The peptide’s sequence is highly conserved across mammals, suggesting an evolutionarily maintained signaling role in metabolic regulation.

Why MOTS-c’s Mitochondrial Origin Matters

Most peptide hormones and signaling molecules are encoded in the nuclear genome. MOTS-c’s mitochondrial origin makes it a direct readout of mitochondrial functional state — when mitochondrial stress increases, MOTS-c production and nuclear translocation increase, activating AMPK and downstream metabolic reprogramming. This creates a signaling axis that bypasses conventional nuclear-encoded hormonal pathways. Researchers studying mitochondria-to-nucleus (retrograde) signaling, the biology of aging as a function of mitochondrial decline, or AMPK pathway pharmacology use MOTS-c to probe this axis specifically. MOTS-c’s sequence identity is also notable: a single nucleotide polymorphism in the MOTS-c coding region (A1382C) alters peptide structure and has been associated with differential longevity phenotypes in human population studies.

Research Applications

MOTS-c is used in studies examining:

• Mitochondria-to-nucleus retrograde signaling pathways
• AMPK pathway pharmacology and exercise mimetic biology
• Insulin sensitivity and glucose homeostasis in metabolic disease models
• Aging biology — mitochondrial peptide decline as a function of cellular aging
• Longevity genetics — MOTS-c SNP association studies and functional consequences
• Physical performance and metabolic adaptation in aged animal models
• Comparative mitochondrial-derived peptide research (MOTS-c vs humanin vs SHLP series)

Specifications

Reconstitution

MOTS-c arrives as lyophilized powder and must be reconstituted with bacteriostatic water prior to use. Use the formula:

Total mg ÷ Volume added (mL) = Concentration (mg/mL)

Example: 10mg vial + 2mL BAC water = 5mg/mL solution

Reconstituted peptide should be stored at 2–8°C and used within 28–30 days.

Protocol Notes

Published rodent data provides the primary dosing framework. Human data is limited to early pilot studies as of 2024. The original Lee et al. 2015 study and subsequent aging research used systemic administration in aged mouse models. Weight-based dosing is standard in the animal literature.

• Dose range: 0.5–5mg/kg in published rodent studies; human pilot data limited but lower weight-adjusted quantities reported
• Frequency: Daily or every-other-day injection in most animal model protocols
• Study duration: 4–12 weeks in metabolic and aging studies; short-term (1–2 week) protocols used for acute AMPK activation studies

Research Stacks

MOTS-c is commonly paired in research settings with:

• SS-31 — SS-31 is a mitochondria-targeted antioxidant peptide that stabilizes cardiolipin and reduces electron transport chain ROS production; combining SS-31 with MOTS-c, which activates AMPK and regulates mitochondrial bioenergetics, is studied to probe complementary aspects of mitochondrial function and metabolic efficiency in aging and stress models.
• NAD+ — NAD+ is an obligate coenzyme for sirtuin and PARP activity and declines with age; pairing with MOTS-c’s AMPK-mediated metabolic regulation is studied to examine whether restoring NAD+ availability amplifies or interacts with MOTS-c’s effects on glucose metabolism and mitochondrial respiration.
• 5-Amino-1MQ — 5-Amino-1MQ inhibits NNMT (nicotinamide N-methyltransferase), an enzyme that consumes SAM and indirectly depletes NAD+ precursors; researchers pair it with MOTS-c to study coordinated NAD+ conservation and mitochondrial metabolic signaling in metabolic disease models.

Purity Guarantee

Every batch is ≥99% purity. If you independently test your compound and the results don’t match — send us the COA and we’ll issue store credit, no questions asked.