MOTS-C
[CAS# 1627580-64-6]

Identification

• Classification: API >> Inhibitor drug
• Name: MOTS-C
• Synonyms: (4S)-4-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-oxopentanoyl]amino]-5-[[(2S)-1-[[2-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid
• Protein Sequence: MRWQEMGYIFYPRKLR
• Molecular Formula: C₁₀₁H₁₅₂N₂₈O₂₂S₂
• Molecular Weight: 2174.59
• CAS Registry Number: 1627580-64-6
• SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)N

Properties

• Density: 1.33±0.1 g/cm³, Calc.

Discovory and Applicatios

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a small bioactive peptide encoded by the mitochondrial genome, specifically from the 12S rRNA region. It consists of 16 amino acids and was first described in 2015 by researchers investigating nontraditional functions of mitochondrial DNA, especially those involved in signaling pathways between mitochondria and the nucleus. Unlike the conventional understanding of mitochondria as merely cellular powerhouses, the discovery of MOTS-c highlighted their regulatory role in metabolic homeostasis through the expression of peptides acting in an endocrine-like manner.

MOTS-c is produced in the mitochondria and has the unique ability to translocate to the nucleus under conditions of metabolic stress, where it regulates gene expression to promote cell survival and energy balance. This peptide has been shown to enhance insulin sensitivity, promote glucose uptake, and regulate fatty acid oxidation, primarily by activating AMP-activated protein kinase (AMPK), a key energy-sensing enzyme in cells. Through AMPK signaling, MOTS-c adjusts cellular metabolism in response to energy stress, supporting its proposed function as a mitochondrial-encoded hormone-like molecule.

In preclinical studies, MOTS-c has demonstrated protective effects against metabolic disorders. Animal models have shown that administration of MOTS-c improves glucose tolerance, increases insulin sensitivity, and prevents diet-induced obesity. These effects have made it a promising candidate for therapeutic development in conditions such as type 2 diabetes, obesity, and metabolic syndrome. Additionally, MOTS-c has been associated with anti-inflammatory and cytoprotective actions, which are relevant in the context of age-related diseases.

Emerging research suggests that MOTS-c may also play a role in promoting longevity and resistance to age-associated metabolic decline. In aging animal models, MOTS-c levels decline, and replenishment through peptide administration has been observed to restore metabolic function and physical performance. These findings have sparked interest in its potential use in age-related interventions, though human data remain limited.

MOTS-c also appears to have effects on muscle physiology. It has been reported to enhance skeletal muscle function and endurance by optimizing energy utilization and mitochondrial biogenesis. These properties have led to speculation about its role in physical performance and recovery. However, the peptide is not currently approved for any medical or therapeutic use and is predominantly used in experimental settings.

To date, MOTS-c has not been evaluated in large-scale clinical trials, and its long-term safety and efficacy in humans remain undetermined. Most studies have been conducted in vitro or in rodent models, with a few preliminary investigations involving human cell cultures or small cohorts. As such, while its biological activity and potential therapeutic benefits are supported by growing preclinical data, further validation through rigorous clinical testing is necessary before MOTS-c can be translated into clinical use.

MOTS-c belongs to a broader class of peptides termed mitochondrial-derived peptides (MDPs), which represent a novel frontier in understanding mitochondrial signaling and its influence on systemic physiology. Alongside other MDPs such as humanin and SHLPs (small humanin-like peptides), MOTS-c exemplifies the expanding functional repertoire of the mitochondrial genome beyond its traditional role in energy production.

In summary, MOTS-c is a mitochondrial-encoded peptide with verified roles in regulating metabolic homeostasis, enhancing insulin sensitivity, and promoting cellular adaptation to stress. It holds significant potential as a therapeutic agent for metabolic and age-related disorders, although its application in medicine remains at the investigational stage. The discovery of MOTS-c has provided valuable insight into mitochondria-to-nucleus communication and expanded the scope of mitochondrial biology in health and disease.