The field of mitochondrial peptides has identified two different compounds that address different ways to boost mitochondrial function and address cellular energy metabolism challenges. MOTS-c, a naturally occurring mitochondrial derived peptide, and SS-31, a synthetic mitochondrial-targeting compound, are the leading subjects in preclinical studies for mitochondrial dysfunction and age related diseases.
Research shows these peptides work through different molecular mechanisms while targeting overlapping pathways for cellular health and energy production. To understand the pros and cons of MOTS-c vs SS-31, we need to look at their molecular composition, research applications and mechanisms of action in the lab.
What are MOTS-c and SS-31 Peptides
MOTS-c is a 16 amino acid mitochondrial derived peptide encoded by the mitochondrial 12S rRNA gene. Unlike traditional nuclear encoded proteins, this peptide mots c comes from the mitochondrial genome, challenging the conventional understanding of mitochondria’s regulatory capabilities. Research shows MOTS-c can regulate nuclear gene expression and affect systemic metabolic processes in animal models.
SS-31, also known as Elamipretide, is a synthetic approach to mitochondrial protection. This tetrapeptide was designed to target cardiolipin, a unique phospholipid in the inner mitochondrial membrane. Studies show SS-31 can cross the blood brain barrier, making it useful for research into neurodegenerative diseases and cardiovascular disease.
The discovery timeline is important to understand the history of these compounds. SS-31 was developed from targeted drug design post 2000, while MOTS-c was identified more recently as genomic tools became available to study mitochondrial derived peptides. Both have gone through extensive preclinical studies, with SS-31 further into clinical trials.
The differences in their origin reflect different research philosophies: MOTS-c uses the body’s natural mitochondrial signaling, while SS-31 uses synthetic chemistry to create highly specific mitochondrial targeting. This fundamental difference impacts their mechanisms, applications and research directions.
Molecular Composition and Chemical Data
The molecular structure of MOTS-c vs SS-31 shows significant differences that impact their biological activities. MOTS-c is a 16 amino acid peptide with the sequence MRWQEMGYIFYPRKLR, encoded directly from the mitochondrial 12S rRNA gene region. This natural peptide is conserved across 14 mammalian species, indicating evolutionary importance in metabolic homeostasis regulation.
Research shows MOTS-c has a molecular weight of approximately 1,915 daltons and is stable under physiological conditions. The peptide structure allows for rapid cellular uptake and distribution, especially in skeletal muscle where it affects glucose metabolism and muscle function through amp activated protein kinase pathways.
SS-31 is a more compact tetrapeptide with the sequence D-Arg-dimethylTyr-Lys-Phe-NH2. With a molecular weight of approximately 640 daltons, this compound was designed for optimal cardiolipin binding in the mitochondrial membrane structure. The synthetic design incorporates modified amino acids for enhanced stability and membrane permeability.
Property | MOTS-c | SS-31 |
|---|---|---|
Amino Acid Length | 16 | 4 |
Molecular Weight | ~1,915 Da | ~640 Da |
Origin | Natural (mitochondrial genome) | Synthetic |
Primary Target | Nuclear genes, AMPK pathway | Cardiolipin, mitochondrial membrane |
Bioavailability | High tissue distribution | Enhanced membrane penetration |
Bioavailability studies show different administration characteristics for each compound. MOTS-c shows rapid distribution to skeletal muscle and other metabolically active tissues, while SS-31 has unique membrane-penetrating properties to target mitochondria directly. These differences impact experimental protocols and research applications in the lab.
Research Areas for MOTS-c vs SS-31
Research applications for MOTS-c focus primarily on metabolic disorders and age related diseases. Preclinical studies have extensively studied its effects on insulin resistance, with research showing significant improvement in glucose uptake and glucose homeostasis in mouse skeletal muscle models. Scientists have particularly looked at its potential as an exercise mimetic, with studies showing improved fatigue resistance and metabolic stress responses.
Clinical studies on MOTS-c have investigated its role in obesity and insulin resistance, with researchers seeing improvement in inflammatory markers and reduction in tumor necrosis factor alpha in experimental models. The peptide’s ability to regulate metabolic homeostasis makes it of interest for age dependent physical decline and metabolic syndrome research.SS-31 research focuses on mitochondrial dysfunction in cardiovascular disease and neurodegenerative diseases. Clinical trials have looked at its use in mitochondrial myopathies, with research showing protective effects against oxidative stress and improved mitochondrial bioenergetics. The compound’s ability to maintain membrane integrity makes it useful for studying damage prevention.
Current clinical trial status shows SS-31 in more advanced phases, with ongoing studies in primary mitochondrial diseases and cardiac conditions. MOTS-c is still in preclinical development, but early phase human studies are starting to look at its metabolic effects. Both have promise for age related diseases but through different mechanisms.
Research into athletic performance and recovery has shown interesting differences. MOTS-c treatment has shown improved exercise capacity and muscle homeostasis in animal models, while SS-31 has shown protection against exercise induced oxidative stress. These findings suggest complementary applications in sports science.
Mechanism of Action Comparison
The mechanism of action differences between MOTS-c vs SS-31 represent different approaches to mitochondrial enhancement. MOTS-c works through a complex pathway involving folate metabolism and AICAR mediated AMPK activation. Research shows that under metabolic stress, MOTS-c can translocate from mitochondria to the nucleus where it regulates nuclear gene expression related to cellular energy metabolism.
Studies show MOTS-c increases glucose metabolism by increasing GLUT4 expression and improving insulin sensitivity at the cellular level. This mechanism mimics caloric restriction and exercise, so researchers are looking at it as a metabolic modulator. The peptide’s effect on the electron transport chain is indirect, working through transcription factors that enhance mitochondrial biogenesis and oxidative phosphorylation capacity.
SS-31 works through direct binding to cardiolipin in the mitochondrial membrane. This interaction stabilizes the inner mitochondrial membrane structure and optimizes electron transport efficiency. Research shows SS-31 can reduce reactive oxygen species production by 40-60% in stressed cellular models while improving ATP synthesis and cellular energy output.
The cardiolipin binding mechanism of SS-31 provides immediate mitochondrial protection during oxidative stress. Studies show this binding preserves mitochondrial dynamics and prevents membrane permeabilization that can lead to cellular senescence. Unlike MOTS-c’s regulatory approach, SS-31 is a direct structural stabilizer of mitochondrial architecture. Cellular target differences show complementary mechanisms: MOTS-c affects skeletal muscle and nuclear signaling pathways while SS-31 acts on mitochondrial membranes across various tissue types. Research shows MOTS-c’s effects take hours to days to develop as gene expression changes occur while SS-31 provides immediate mitochondrial benefits upon administration.
Comparative Benefits and Clinical Applications
Research comparing MOTS-c vs SS-31 shows different therapeutic profiles for different applications. MOTS-c studies consistently show improved glucose metabolism with preclinical models showing up to 30% increase in glucose uptake and significant reduction in insulin resistance markers. Research suggests this is due to the peptide’s ability to enhance glucose metabolism through AMPK activation and muscle homeostasis.
Circulating mots c levels in experimental subjects correlate with improved metabolic parameters, including reduced inflammatory responses and increased fat oxidation. Studies looking at plasma mots c levels show inverse relationship with obesity markers and positive association with exercise capacity. The peptide’s effects on aging cell populations suggest applications in cellular senescence research.
SS-31 research shows remarkable mitochondrial protection, with studies showing preserved mitochondrial bioenergetics under stress conditions. Research shows SS-31 can prevent pancreatic islet destruction in autoimmune diabetes models and reduce cellular damage in chronic kidney disease experimental settings. The compound’s ability to maintain electron transport efficiency makes it useful for studying mitochondrial dysfunction in various disease models.
Synergistic potential emerges when considering MOTS-c vs SS-31 in combination protocols. Research suggests SS-31’s immediate mitochondrial protection could complement MOTS-c’s longer term metabolic optimization. Studies looking at combined approaches show enhanced benefits compared to individual compound administration, especially in metabolic stress and aging related decline.
Safety profiles from preclinical studies show good tolerability for both compounds. MOTS-c research shows minimal adverse effects in long term administration studies while SS-31 shows good safety margins in clinical trial settings. Both peptides work with natural cellular processes rather than disrupting normal physiology.
Future Research Directions for Both Peptides
Ongoing research into MOTS-c vs SS-31 will continue to expand our understanding of mitochondrial targeted interventions. Current clinical trials are looking at optimal dosing and biomarkers for treatment response. Research suggests personalized approaches based on individual mitochondrial function assessments may optimize treatment outcomes for both compounds.Combination therapy protocols are a promising research direction. Studies are looking at how MOTS-c’s metabolic regulation can synergize with SS-31’s membrane protection to provide full mitochondrial support. Early research shows that sequential or concurrent administration can address immediate protection needs and long term metabolic optimization.
Synthetic biology is advancing MOTS-c research with scientists working on modified versions that enhance stability or target specificity. Research is focused on delivering to specific tissues while maintaining the peptide’s natural regulatory properties. This will expand research applications and improve experimental reproducibility.
SS-31 optimization is ongoing through structure-activity relationship studies to enhance cardiolipin binding specificity. Research suggests that modifications to the synthetic structure can improve selectivity for damaged mitochondria while reducing effects on healthy cells. This will increase the compound’s therapeutic window in experimental applications.
Long term safety studies are a priority for both compounds as research moves towards clinical applications. Ongoing studies are looking at chronic administration effects, resistance development and optimal treatment duration protocols. These will inform future research guidelines and safety parameters.
Purchase MOTS-c and SS-31 at Loti Labs
Loti Labs offers research grade MOTS-c with verified purity standards above 98% as determined by HPLC analysis. Available in lyophilized powder presentations for reconstitution in various research applications. Each batch is tested by third party to ensure molecular integrity and absence of contaminants that can affect experimental outcomes.
SS-31 peptide options at Loti Labs are pharmaceutical grade with detailed COA documenting purity, molecular weight confirmation and stability data. Available in multiple quantities to fit small scale research projects or larger experimental protocols.
Pricing reflects the complexity of peptide synthesis and purification process. MOTS-c pricing accounts for the sophisticated production methods to maintain natural peptide integrity, while SS-31 pricing reflects synthetic optimization and quality control. Bulk purchase options available for extended research protocols or multi-experiment studies.
Quality assurance protocols ensure both peptides meet research standards. Storage requirements include specific temperature controls and moisture protection to maintain peptide stability throughout the research period. Handling protocols are provided with each shipment to optimize experimental results.
Shipping is designed to accommodate the sensitive nature of peptide compounds with temperature controlled delivery options and expedited processing for time sensitive research applications. Documentation is provided with each shipment detailing storage recommendations and handling procedures to maintain compound integrity from delivery to use.
Summary
The comparison of MOTS-c vs SS-31 shows two different but potentially complementary approaches to mitochondrial research applications. MOTS-c as a naturally occurring mitochondrial derived peptide offers insight into how endogenous mitochondrial signaling regulates nuclear gene expression and metabolic homeostasis. Research shows its value in insulin resistance, aging related metabolic decline and exercise physiology studies.
SS-31’s synthetic design provides targeted mitochondrial membrane protection through cardiolipin binding, making it useful for research into acute mitochondrial dysfunction and oxidative stress damage. Clinical trials have advanced its development for mitochondrial diseases and cardiovascular research, while preclinical studies are exploring its neuroprotective potential.
The molecular mechanisms of MOTS-c vs SS-31 suggest they address different aspects of mitochondrial health: MOTS-c focuses on metabolic regulation and gene expression while SS-31 provides direct structural protection and bioenergetic optimization. This makes them useful for different research questions and experimental designs.
Future research will look into combination approaches that leverages both peptides’ strengths. Studies show that SS-31’s immediate protection can complement MOTS-c’s long term metabolic improvements, potentially providing full mitochondrial support in aging and disease models.
For researchers choosing between these compounds consider your research objectives: MOTS-c for metabolic and aging studies, SS-31 for mitochondrial dysfunction and protection research, or combination protocols for full mitochondrial investigation. Both peptides offer unique insights into mitochondrial biology and therapeutic potential.
The complementary nature of MOTS-c vs SS-31 reflects the growing understanding that mitochondrial health requires both structural integrity and metabolic optimization. As research advances our knowledge of these compounds, their applications in research will expand, providing new tools to understand cellular energy metabolism and age related changes.
References
- Lee, C., et al. (2015). “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” Cell Metab 21(3): 443-454.
- Reynolds, J.C., et al. (2021). “MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.” Nature Communications 12(1): 470.
- Szeto, H.H. (2014). “First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics.” British Journal of Pharmacology 171(8): 2029-2050.4. Birk, A.V., et al. (2013). “SS-31 re-energizes ischemic mitochondria by binding to cardiolipin.” J Am Soc Nephrol 24(8): 1250-1261.
- Chatfield, K.C., et al. (2019). “Elamipretide improves mitochondrial function in heart and skeletal muscle in Barth syndrome.” J Clin Invest 129(8): 3129-3143.
- Kim, K.H., et al. (2018). “Mitochondrial peptides in aging and age-related diseases.” GeroScience 40(2): 113-119.
- D’Angelo, S., et al. (2020). “Mitochondrial peptides in cardiovascular disease and aging.” Front Physiol 11: 590918.
- Ming, W., et al. (2021). “MOTS-c rescues ovariectomy-induced bone loss by promoting bone formation.” Biochem Biophys Res Commun 561: 74-80.
- Dabravolski, S.A., et al. (2022). “Mitochondrial peptides in cardiovascular diseases and as therapeutic targets.” Int J Mol Sci 23(11): 6062.
