MOTS-cAlso known as: Mitochondrial ORF of the 12S rRNA-c, MOTS-C peptide

Mechanism of Action

MOTS-c is a mitochondrial-derived peptide that modulates metabolic homeostasis primarily through activation of the AMP-activated protein kinase (AMPK) pathway. This activation promotes energy balance by enhancing glucose uptake, fatty acid oxidation, and regulating insulin sensitivity. It also plays a protective role against metabolic stress by improving mitochondrial function and cellular resilience.

Reported Research Benefits

MOTS-c is investigated in research contexts involving metabolic regulation, insulin sensitivity improvement, glucose metabolism, obesity, mitochondrial dysfunction, muscle endurance, and anti-aging mechanisms. It is used to study effects on energy balance, metabolic flexibility, and cell protection in preclinical models.

Dosing Protocol & Reconstitution

MOTS-c is supplied in lyophilized powder form and is reconstituted with bacteriostatic water for laboratory use. Typical experimental dosing involves subcutaneous injection using insulin syringes for precise delivery. Stability after reconstitution requires refrigerated storage (2–8°C) with a usable shelf life up to 60 days. Research doses commonly range from 5 to 20 mg/kg in animal studies but vary based on experimental design.

Research Notes

Preclinical studies show MOTS-c enhances metabolic flexibility, protects against insulin resistance, and improves mitochondrial function. It has been linked to better muscle endurance and reduced adiposity in animal models. The peptide's half-life in vivo is relatively short (minutes to hours), necessitating controlled dosing protocols in research settings.

Research Summary

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a mitochondria-encoded peptide that acts as an exercise-mimetic by activating AMPK and regulating folate and methionine cycles. It improves insulin sensitivity, promotes fat utilization, and demonstrates anti-aging effects in aged mouse models including improved muscle function. Plasma levels naturally decline with age.

Side Effects & Safety

Preclinical studies show excellent tolerability. No significant adverse events in animal models. Human data is very limited; it is considered an emerging research compound. Potential interactions with folate pathway metabolism warrant further study.

Stability & Storage

Refer to research notes

Molecular Data

Sequence: MRWQEMGYIFYPRKLR
Molecular Formula: C109H172N28O31S
Molecular Weight: 2174.77 g/mol
CAS Number: 1229963-42-7
IUPAC Name: N-((1S)-1-(((2S)-2-(methionylamino)-3-(4-hydroxyphenyl)propanamido)-3-(4-hydroxyphenyl)propanamido)-1-oxo-3-phenylpropan-2-yl)glycyl-L-prolyl-L-lysyl-L-arginyl-L-leucyl-L-arginyl

Primary literature: https://pubmed.ncbi.nlm.nih.gov/?term=MOTS-c+mitochondria+AMPK+metabolism