SS-31
Also known as: Elamipretide, Bendavia, MTP-131, D-Arg-Dmt-Lys-Phe-NH2
SS-31 (Elamipretide) is a mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane. It stabilizes cardiolipin, optimizes electron transport chain efficiency, and reduces mitochondrial ROS production. Developed for mitochondrial diseases and heart failure, it represents a new class of mitochondrial medicine.
SS-31 is a 615.77 Da research peptide. SS-31 (Elamipretide) is a mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane. It stabilizes cardiolipin, optimizes electron transport chain efficiency, and reduces mitochondrial ROS production. Developed for mitochondrial diseases and heart failure, it represents a new class of mitochondrial medicine.
Also called: Elamipretide, Bendavia, MTP-131
615.77
Molecular Weight
Daltons
3
Strong Evidence
benefits
5
Studies Cited
peer-reviewed
4000-4000
Typical Dose
mcg
Overview
SS-31 (Elamipretide) is a synthetic cell-permeable tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2, where Dmt = 2',6'-dimethyltyrosine) that selectively concentrates in the inner mitochondrial membrane at 1,000-5,000x higher concentration than in the cytoplasm. It was developed by Hazel Szeto and Peter Bhatt at Cornell University as part of the Szeto-Schiller (SS) peptide series designed to target mitochondria. Unlike conventional antioxidants that scavenge free radicals after they are formed, SS-31 works at the source; it binds cardiolipin (a phospholipid unique to the inner mitochondrial membrane essential for cristae structure and electron transport chain organization) and stabilizes its interaction with cytochrome c. This prevents electron leak from Complex III, reduces mitochondrial reactive oxygen species (ROS) production at the source, and optimizes ATP synthesis. SS-31 has been in clinical development by Stealth BioTherapeutics (now Larimar Therapeutics and others) as Elamipretide for Barth syndrome, primary mitochondrial myopathy, age-related macular degeneration, and heart failure. Phase II/III trials have shown improvements in exercise capacity, cardiac function, and mitochondrial biomarkers. It represents a change from conventional antioxidants to targeted mitochondrial optimization.
Key Takeaways: SS-31
- Strongest evidence supports SS-31 for mitochondrial ros reduction at source and atp synthesis optimization
- Research doses typically range from 4000 to 4000 mcg via subcutaneous injection
- 3 benefits with strong evidence, 3 moderate, 0 preliminary
- Half-life: ~4 hours (subcutaneous); tissue accumulation provides extended mitochondrial effects
- 5 cited research studies in this guide
Mechanism of Action
SS-31's alternating aromatic-cationic motif (D-Arg-Dmt-Lys-Phe) enables cell membrane penetration without requiring transporter proteins and selective accumulation in the inner mitochondrial membrane driven by the mitochondrial membrane potential. Once there, SS-31 binds cardiolipin, a unique tetra-acyl phospholipid found exclusively in the inner mitochondrial membrane. Cardiolipin is essential for cristae morphology, respiratory supercomplex organization, and the interaction between cytochrome c and Complex III/IV. With aging and disease, cardiolipin undergoes peroxidation and structural changes, disrupting electron transport chain organization and increasing electron leak (producing superoxide). SS-31 stabilizes cardiolipin's interaction with cytochrome c, maintaining proper electron transfer between Complexes III and IV and preventing electron leak to molecular oxygen. This reduces mitochondrial ROS production at the source (not by scavenging) while simultaneously improving ATP synthesis efficiency — a dual benefit that conventional antioxidants cannot achieve. SS-31 also preserves cristae ultrastructure, prevents mitochondrial permeability transition pore (mPTP) opening, and reduces cytochrome c release (anti-apoptotic). The net effect is restored mitochondrial bioenergetics: more ATP with less oxidative damage.
Research Benefits
SS-31 at a Glance
SS-31's alternating aromatic-cationic motif (D-Arg-Dmt-Lys-Phe) enables cell membrane penetration without requiring transporter proteins and selective accumulation in the inner mitochondrial membrane driven by the mitochondrial membrane potential.
Mitochondrial ROS Reduction at Source
Strong EvidenceReduces superoxide production at the electron transport chain by stabilizing electron flow through Complex III, preventing electron leak, fundamentally different from conventional antioxidant scavenging.
ATP Synthesis Optimization
Strong EvidenceImproves mitochondrial coupling efficiency, increasing ATP production per unit oxygen consumed. Clinical trials show improved exercise capacity and cardiac energetics.
Cardiolipin Stabilization
Strong EvidenceDirectly binds and stabilizes cardiolipin in the inner mitochondrial membrane, preserving cristae structure and respiratory supercomplex organization.
Heart Failure Improvement
Moderate EvidencePhase II trials in heart failure with reduced ejection fraction showed improved left ventricular volumes and cardiac energetics with elamipretide treatment.
Barth Syndrome Treatment
Moderate EvidenceClinical trials in Barth syndrome (genetic cardiolipin deficiency) showed improved exercise capacity, cardiac function, and patient-reported outcomes.
Age-Related Mitochondrial Decline
Moderate EvidencePreclinical studies show SS-31 reverses age-related mitochondrial dysfunction in skeletal muscle, heart, brain, and kidney; restoring youthful bioenergetic profiles.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| Clinical trial dose (heart failure) | 4000–4000 mcg | Subcutaneous injection |
| Barth syndrome clinical trials | 40000–40000 mcg | Subcutaneous injection daily |
| Research/optimization protocols | 1000–5000 mcg | Subcutaneous injection |
Frequency
Once daily (clinical trials); some research protocols use loading approaches
Timing
No strict timing; some research protocols dose pre-exercise for performance applications
Cycle Length
Clinical trials: 4 weeks to 6 months continuous treatment
Research Notes
- 1SS-31 concentrates 1,000-5,000x in mitochondria vs. cytoplasm.
- 2Cell-permeable — does not require mitochondrial targeting sequences or carriers.
- 3Effects on mitochondrial function are measurable within hours; structural benefits accumulate over weeks.
- 4Not yet FDA-approved; multiple Phase II/III trials completed and ongoing.
- 5Developed by Stealth BioTherapeutics (now under Larimar Therapeutics and successor companies).
- 6Fundamentally different from conventional antioxidants, works at the source of ROS production.
Reconstitution Guide
Standard Reconstitution
Vial Size
10 mg
Bacteriostatic Water
2 mL
Concentration
50 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
SS-31 vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 2 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at Refrigerated (2-8°C) after reconstitution. Up to 30 days refrigerated.
Storage Temperature
Refrigerated (2-8°C) after reconstitution
Shelf Life
Up to 30 days refrigerated
Important Notes
- •Reconstitute with bacteriostatic water or sterile water.
- •Contains D-amino acid (D-Arg) — protease resistant.
- •Relatively stable tetrapeptide.
- •Store lyophilized powder at -20°C for long-term storage.
SS-31 Dosing Calculator
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SS-31 Reconstitution Calculator
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Safety & Side Effects
Reported Side Effects
- !Injection site reactions (most common in clinical trials)
- !Headache
- !Dizziness (infrequent)
- !Nausea (mild, infrequent)
- !Generally well tolerated in Phase II/III clinical trials
- !No significant safety signals identified in clinical development
Potential Interactions
- ⚡Theoretical additive effects with other mitochondrial support agents (CoQ10, NAD+ precursors).
- ⚡No significant drug interactions identified in clinical trials.
- ⚡May complement exercise-induced mitochondrial biogenesis.
- ⚡Compatible with standard heart failure medications in clinical trials.
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
SS-31 targets cardiolipin and improves mitochondrial bioenergetics
Established SS-31's mechanism of action: selective binding to cardiolipin in the inner mitochondrial membrane, stabilizing cytochrome c interaction, reducing ROS, and improving ATP synthesis.
Elamipretide in heart failure with reduced ejection fraction (Phase II)
Phase II trial showing elamipretide improved left ventricular end-systolic volume and NT-proBNP levels in heart failure patients, demonstrating cardiac benefit from mitochondrial targeting.
SS-31 reverses age-related mitochondrial dysfunction in skeletal muscle
Demonstrated SS-31 rapidly reverses age-related mitochondrial dysfunction in mouse skeletal muscle, restoring ATP production and reducing oxidative damage within one hour of treatment.
Elamipretide for Barth syndrome: clinical trial results
Clinical trial in Barth syndrome showing elamipretide improved six-minute walk test distance, cardiac stroke volume, and patient-reported outcomes in this genetic mitochondrial disease.
Mitochondria-targeted peptides: the SS peptide platform
thorough review by the developer of SS peptides covering the rationale for mitochondrial targeting, cardiolipin biology, and the therapeutic potential of SS-31 across multiple disease contexts.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
SS-31 (Elamipretide) is a mitochondria-targeted tetrapeptide that concentrates in the inner mitochondrial membrane, stabilizes cardiolipin, reduces ROS production at the electron transport chain, and improves ATP synthesis. It is being developed for heart failure, Barth syndrome, and mitochondrial diseases.
Conventional antioxidants scavenge free radicals after they are formed. SS-31 prevents ROS from being produced in the first place by stabilizing electron flow through the respiratory chain. This is a fundamentally different approach, reducing oxidative damage at the source while also improving energy production.
SS-31's alternating aromatic-cationic structure enables cell membrane penetration, and the strong negative membrane potential of mitochondria (-180mV) drives selective accumulation in the inner mitochondrial membrane at 1,000-5,000x concentration.
Not yet. Elamipretide has completed Phase II/III trials for Barth syndrome, heart failure, and other conditions. It received Breakthrough Therapy and Fast Track designations from the FDA but has not yet received final approval.
Preclinical data is striking; SS-31 reverses age-related mitochondrial dysfunction in multiple tissues within hours. Whether this translates to meaningful lifespan or healthspan extension in humans is an active area of research. It is one of the most promising anti-aging compounds in clinical development.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.