What Is SS-31 (Elamipretide)?

SS-31, also known as Elamipretide (brand name MTP-131), is a synthetic aromatic-cationic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂ (molecular weight 639.8 g/mol). It was developed by Hazel Szeto and Peter Schiller at Weill Cornell Medicine — giving rise to the ‘SS’ naming convention (Szeto-Schiller). Among research peptides, SS-31 stands apart for one defining physical property: it concentrates approximately 1,000-fold in the inner mitochondrial membrane (IMM) due to the alternating aromatic and cationic residues in its structure, which interact with the IMM’s unique negative charge potential.

This extraordinary IMM selectivity makes SS-31 one of the most specific mitochondria-targeted research tools available. Its primary site of action — cardiolipin, the signature phospholipid of the IMM — distinguishes it from all other longevity and metabolic research peptides. QSC stocks SS-31 Elamipretide at ≥99% HPLC purity with Janoshik independent COA, verifiable at verify.janoshik.com.

The Cardiolipin Mechanism

Cardiolipin is a structurally unique phospholipid found almost exclusively in the inner mitochondrial membrane. Unlike all other cellular phospholipids, cardiolipin has four acyl chains and two phosphate groups — a structure that makes it an ideal scaffold for the cristae architecture and ETC supercomplex assembly.

Why Cardiolipin Is the Key to Mitochondrial Function

• Cristae stabilisation: Cardiolipin maintains the highly folded inner membrane architecture (cristae) that dramatically increases the surface area for ATP synthesis. Loss of cardiolipin flattens cristae, reducing ATP output.
• ETC supercomplex assembly (‘respirasomes’): Complexes I, III, and IV are held together in supercomplexes by cardiolipin. Supercomplex integrity improves electron transfer efficiency and reduces reactive oxygen species (ROS) leak.
• Cytochrome c retention: Cardiolipin binds cytochrome c in the IMM. When cardiolipin is oxidised, cytochrome c is released into the cytoplasm — a direct trigger of the mitochondrial apoptosis pathway.
• Proton gradient maintenance: Cardiolipin acts as a proton trap, concentrating H⁺ ions near Complex V (ATP synthase) to maintain the electrochemical gradient (ΔΨm) required for oxidative phosphorylation.

How SS-31 Protects Cardiolipin

SS-31 binds directly to cardiolipin via electrostatic and hydrophobic interactions. The D-Arg and Lys residues (cationic) anchor to cardiolipin’s phosphate groups; the Dmt (2′,6′-dimethyltyrosine) and Phe residues (aromatic) insert into the lipid bilayer. This binding prevents cardiolipin peroxidation by cytochrome c peroxidase activity — the primary mechanism of cardiolipin oxidation in stressed mitochondria. ^[1]

The consequences of preserved cardiolipin integrity in SS-31 research models include: restored cristae structure, improved Complex I–IV activity, reduced cytochrome c release, and maintained ΔΨm under stress conditions. ^[2]

Inner Mitochondrial Membrane Architecture

To understand why SS-31 research is significant, it helps to understand what the IMM does and why its integrity declines with age, ischemia, and mitochondrial disease.

Phase 2 Clinical Data Overview

SS-31 (as pharmaceutical Elamipretide, Stealth BioTherapeutics) has been evaluated in multiple Phase 2 human clinical trials. The following data pertains to the pharmaceutical compound — not QSC’s research-grade supply, which is for in vitro use only.

HOPEFUL-1: Heart Failure with Preserved Ejection Fraction (HFpEF)

HOPEFUL-1 was a randomised, double-blind, placebo-controlled Phase 2 trial of subcutaneous Elamipretide in patients with HFpEF (n=71). Primary endpoint: change in 6-minute walk distance (6MWD) at 28 days. Results showed a statistically significant improvement in 6MWD vs placebo (+21m, p=0.026) and improvement in left ventricular end-systolic volume index. ^[3]

Barth Syndrome

Barth syndrome is a rare X-linked mitochondrial cardiomyopathy caused by mutation in the tafazzin gene — directly impairing cardiolipin remodelling. Phase 2 data showed improvements in 6MWD, hand grip strength, and Patient Global Assessment in Elamipretide-treated patients vs placebo, with a manageable safety profile. ^[4]

Mitochondrial Myopathy

A Phase 2 trial in primary mitochondrial myopathy demonstrated significant improvements in fatigue and motor function endpoints with Elamipretide vs placebo. This trial established Elamipretide’s relevance across mitochondrial disease states beyond cardiomyopathy. ^[5]

SS-31 vs MOTS-c: Complementary Mitochondrial Pathways

SS-31 and MOTS-c are both mitochondria-related research compounds but act through entirely different mechanisms and locations. Together they cover complementary aspects of mitochondrial biology — which is why researchers often study them together as part of the SS-31 + MOTS-c mitochondrial research stack.

Purity Standards and COA Verification

For SS-31 research, COA documentation must include: (1) HPLC chromatogram confirming ≥99% target peak area; (2) mass spectrometry confirmation at 639.8 g/mol ±0.5 Da; (3) net peptide content (NPC) — the fraction of vial weight that is actual peptide. QSC submits every SS-31 batch to Janoshik (independent Czech analytical laboratory) before sale. Results are publicly verifiable at verify.janoshik.com by batch code. See Understanding Peptide Purity: HPLC vs MS for a full guide to evaluating research peptide COAs.

Frequently Asked Questions

What is SS-31 (Elamipretide) and how does it work?

SS-31, also known as Elamipretide (D-Arg-Dmt-Lys-Phe-NH₂), is a mitochondria-targeted tetrapeptide that concentrates approximately 1,000-fold in the inner mitochondrial membrane (IMM). Its primary mechanism is binding and stabilising cardiolipin — the signature phospholipid of the IMM — which maintains cristae structure, preserves electron transport chain (ETC) complex I/II function, and prevents the apoptotic release of cytochrome c. SS-31 is sold by QSC for in vitro laboratory research only.

What is the difference between SS-31 and MOTS-c?

SS-31 (Elamipretide) acts at the inner mitochondrial membrane via cardiolipin binding, primarily protecting cristae structure and ETC function. MOTS-c is a 16-amino acid peptide encoded in the mitochondrial 12S rRNA gene that acts cytoplasmically via AMPK activation, upregulating glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. Both are mitochondria-focused, but via completely independent mechanisms. QSC stocks both at ≥99% HPLC with Janoshik independent COA.

What clinical trial data exists for SS-31?

SS-31 (as Elamipretide, Stealth BioTherapeutics) has Phase 2 data in: (1) HOPEFUL-1 — heart failure with preserved ejection fraction (HFpEF), showing improvement in 6-minute walk distance vs placebo; (2) Barth syndrome — rare mitochondrial cardiomyopathy, showing improved motor function and cardiac outcomes; (3) mitochondrial myopathy. Phase 3 trials have been initiated. All clinical data pertains to pharmaceutical Elamipretide. QSC supplies SS-31 for in vitro research only.

What is cardiolipin and why does it matter for mitochondrial function?

Cardiolipin is a unique, double-phosphate phospholipid found almost exclusively in the inner mitochondrial membrane. It stabilises the cristae architecture, anchors ETC complexes (I, III, IV) in supercomplexes (‘respirasomes’), and acts as a proton trap that maintains the electrochemical gradient for ATP synthesis. In aging, ischemia, and mitochondrial disease, cardiolipin is oxidised and reduced — a central mechanism of mitochondrial dysfunction. SS-31 binds cardiolipin and prevents its oxidation.

Where can I buy SS-31 Elamipretide for research?

QSC (qsc-eu.com) stocks SS-31 Elamipretide at ≥99% HPLC purity with Janoshik independent COA, verifiable at verify.janoshik.com by batch code. Sold for in vitro laboratory research only. Not for human consumption.

References

1. Szeto HH. (2011). Stealth peptides target cellular powerhouses and hold promise for treatment of heart failure. AAPS J. PMID 21383294.
2. Birk AV et al. (2015). Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br J Pharmacol. PMID 26271532.
3. Daubert MA et al. (2020). Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. JACC Heart Fail. PMID 32220193. (HOPEFUL-1)
4. Thompson WR et al. (2021). A Phase 2/3 Randomized Clinical Trial Followed by an Open-Label Extension to Evaluate the Effectiveness of Elamipretide in Barth Syndrome. JACC Heart Fail. PMID 32777260.
5. Karaa A et al. (2018). Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. PMID 33428803.
6. Google Search Central. Creating Helpful, Reliable, People-First Content. Updated December 2025.