MOTS-c: 20 mg ($40)
Overview
MOTS-c is a natural peptide encoded in human mitochondrial DNA that acts as a cellular metabolic regulator. In animal models it has been studied for effects on glucose and fat metabolism, insulin sensitivity, and exercise capacity, and it responds to metabolic stress in ways that have earned it the description of an “exercise mimetic” in the research literature. It is a short peptide belonging to a small class of molecules that overturned a long-standing assumption about what mitochondrial DNA does.
In plain terms
Mitochondria are the structures inside cells that convert fuel into usable energy. Unusually, they carry their own small loop of DNA, separate from the DNA in the cell nucleus. For decades that mitochondrial DNA was understood to encode only components of the energy-production machinery itself.
MOTS-c was among the discoveries that changed that picture. It is encoded within a mitochondrial gene, and rather than staying put and doing local work, the peptide can move to the cell nucleus and influence which nuclear genes are switched on. That makes it a signal traveling in the unexpected direction — from the mitochondria outward to the rest of the cell, rather than the cell issuing instructions inward. Research attention has focused on how that signal behaves under metabolic stress, since it appears to be responsive to the cell's energy state.
Technical description
MOTS-c (mitochondrial open reading frame of the twelve S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the MT-RNR1 (12S rRNA) region of the mitochondrial genome.
Reported mechanism centers on activation of AMP-activated protein kinase (AMPK) and modulation of the folate–methionine cycle and de novo purine biosynthesis, with downstream accumulation of AICAR. Under metabolic stress the peptide undergoes nuclear translocation and associates with stress-responsive transcription factors including ATF1, regulating a nuclear gene program. It is characterized in the literature as a retrograde mitochondrial-to-nuclear signaling molecule. Published data is predominantly from rodent models and cultured cells.
- Full name
- Mitochondrial ORF of the 12S rRNA type-c
- Molecular formula
- C101H152N28O22S2
- Molecular weight
- 2174.6 g/mol
- Sequence
- MRWQEMGYIFYPRKLR
- Encoded by
- MT-RNR1 (mitochondrial 12S rRNA region)
- Primary pathway
- AMPK activation; retrograde nuclear signaling
- Appearance
- White lyophilized powder
- Storage
- Lyophilized: −20 °C, protected from light. Reconstituted: 2–8 °C.
Regulatory status
MOTS-c is not an FDA-approved drug and is not a lawful dietary supplement ingredient. It holds no marketing authorization in any jurisdiction, and it is prohibited by the World Anti-Doping Agency. No human clinical trial has evaluated native MOTS-c itself; the only clinical data comes from CB4211, a structurally modified long-acting analogue developed by CohBar, which completed Phase 1a/1b (NCT03998514) before development was discontinued. Findings from that analogue cannot be assumed to apply to the unmodified peptide. Regulatory classification has been in flux: verify the compound's current standing under FDA compounding review before relying on any statement of status. Material supplied for laboratory research is not manufactured, tested, or released under pharmaceutical standards.