SS-31 (Elamipretide): Mitochondrial Protection, Cardiolipin Stabilization, and Cellular Energy Restoration

A New Frontier in Mitochondrial Medicine

Mitochondria regulate cellular energy, stress responses, redox balance, and metabolic flexibility. As these systems decline with age or metabolic stress, mitochondrial dysfunction becomes a driver of fatigue, impaired tissue repair, and systemic metabolic decline.

SS-31, also known as Elamipretide or MTP-131, is a mitochondria-targeted tetrapeptide designed to selectively target the inner mitochondrial membrane and interact with cardiolipin. By stabilizing mitochondrial structure and reducing oxidative stress, SS-31 has become a leading research tool for studying mitochondrial restoration.

What Is SS-31?

SS-31 is a synthetic mitochondria-targeted tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂.

It can:

• Cross mitochondrial membranes  

• Concentrate at the inner mitochondrial membrane  

• Bind electrostatically to cardiolipin  

• Support mitochondrial architecture and ATP production  

Unlike general antioxidants, SS-31 modulates ROS production at the source while preserving physiological signaling.

Mechanism of Action

1. Cardiolipin Stabilization  

SS-31 binds directly to cardiolipin, helping maintain membrane curvature, respiratory chain structure, and ATP synthesis efficiency.

2. Reduced ROS Production  

By stabilizing membrane architecture, SS-31 reduces "electron leak" that generates excess ROS. This improves redox balance while maintaining physiological signaling.

3. Enhanced ATP Generation  

With more efficient electron flow, SS-31 supports improved mitochondrial energy output and muscular performance.

4. Protection Against Mitochondrial Stress  

SS-31 has been evaluated in models of ischemia-reperfusion injury, age-related decline, metabolic syndrome, and mitochondrial diseases.

Research Highlights

1. Muscle Function and Fatigue  

Improves skeletal muscle endurance, mitochondrial respiration, and ATP turnover.

2. Cardiac Performance  

Supports healthier mitochondrial morphology, reduces oxidative stress, and improves cardiac output in research settings.

3. Age-Related Mitochondrial Decline  

Reverses cardiolipin oxidation, restores respiratory chain stability, and enhances endurance in aging models.

4. Mitochondrial Disorders  

Improves mitochondrial structure and oxygen utilization in studies of mitochondrial pathology.

Cellular Pathways Overview

Function

Primary Mechanism

Research Effect

Membrane Stability

Cardiolipin binding

Maintains mitochondrial structure

Oxidative Control

Reduces electron leak

Lowers pathological ROS

ATP Production

Enhanced electron flow

Improves cellular energy

Muscle Function

Better mitochondrial output

Increased endurance

Redox Homeostasis

Targeted ROS modulation

Protects from oxidative stress

Synergistic Combinations (Research Context)

• MOTS-c — enhances mitochondrial signaling and AMPK activation  

• 5-Amino-1MQ — improves NAD⁺ availability and metabolic pathways  

• NAD⁺ precursors — support sirtuin activity and mitochondrial energy  

• Glutathione — reinforces redox balance during mitochondrial output  

Research Use and Safety

SS-31 has undergone extensive preclinical and early clinical evaluation.

Key points:

• Generally well-tolerated in research environments  

• Effects are most pronounced under mitochondrial stress  

• Not approved for clinical or consumer use  

All descriptions refer strictly to laboratory and research-only contexts.

Summary

SS-31 represents a shift in mitochondrial science toward targeted membrane stabilization. By binding cardiolipin, reducing electron leak, and supporting ATP generation, SS-31 restores a fundamental layer of cellular energy production.

Its effects on muscle function, cardiac resilience, and age-related mitochondrial decline position SS-31 as a central molecule in metabolic and longevity research.

References (Selection)

1. Birk AV, et al. J Am Soc Nephrol. (2013).  

2. Szeto HH. Pharmacology & Therapeutics. (2014).  

3. Zhao K, et al. J Biol Chem. (2004).  

4. Kloner RA, et al. Circulation. (2015).  

5. Dai DF, et al. Aging Cell. (2017).  

Educational & Research Disclaimer

This content is for educational and research purposes only. No medical advice or product claims are implied. Compounds discussed are not approved for human or clinical use and are intended for in-vitro laboratory research only.

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Frequently Asked Questions

Paste under “Frequently Asked Questions (Research Use Only)”

Q1. What is SS-31 (Elamipretide) in research?

SS-31 is a mitochondria-targeted tetrapeptide studied for promoting mitochondrial protection, stabilizing cardiolipin, and supporting cellular energy output in preclinical models.

Q2. How does SS-31 interact with mitochondria in studies?

Research shows SS-31 localizes to the inner mitochondrial membrane, where it binds cardiolipin and may help reduce oxidative stress and improve electron transport efficiency.

Q3. Is SS-31 considered a therapeutic compound?

No. SS-31 from The Peptide Company is intended strictly for laboratory and in-vitro research use and is not approved for human, medical, or clinical use.

Q4. What research applications involve SS-31?

SS-31 is explored in cell and animal models examining mitochondrial dysfunction, bioenergetics, oxidative stress, membrane stability, and aging-related metabolic decline.

Q5. Does SS-31 improve ATP production in studies?

Some preclinical work suggests SS-31 may improve mitochondrial coupling efficiency and ATP output, though these findings remain research-only and non-medical.

Q6. How is SS-31 typically handled in the lab?

Researchers store SS-31 lyophilized in cool, light-protected conditions and reconstitute it following standard laboratory procedures and institutional guidelines.

Q7. Can SS-31 be self-administered?

No. SS-31 is not for human use, self-administration, or consumption of any kind. It is for controlled research environments only.

Related Research Compounds

• MOTS-c – mitochondrial-encoded metabolic regulator

• BAM15 – mitochondrial uncoupler affecting energy expenditure

• 5-Amino-1MQ – NNMT inhibitor for NAD+ and metabolic pathways

  
  

References

PMID: 20378862 — Elamipretide and mitochondrial membrane targeting.

PMID: 24852075 — SS-31 interaction with cardiolipin and membrane stabilizationPMID: 29414749 — Mitochondrial peptide therapeutics in oxidative stress control

PMID: 26975894 — Bioenergetic restoration through mitochondrial protection

PMID: 30559264 — SS-31 effects on electron transport efficiency