What Is SS-31 (Elamipretide)?
SS-31, also known as elamipretide or MTP-131, is a synthetic tetrapeptide belonging to the Szeto-Schiller (SS) peptide family, developed by researchers Hazel Szeto and Peter Schiller. SS-31 has a unique alternating aromatic-cationic amino acid sequence (D-Arg-2′6′-Dmt-Lys-Phe-NH₂) that confers selective affinity for cardiolipin, a phospholipid found almost exclusively in the inner mitochondrial membrane. This mitochondria-targeting property has positioned SS-31 as a widely investigated tool compound in cellular bioenergetics and oxidative stress research. TrueCanPeptides carries SS-31 10mg for laboratory research use.
Learn more about research peptides →
Mechanism of Action
SS-31 selectively concentrates in the inner mitochondrial membrane, where it binds to cardiolipin. Cardiolipin plays a structural and functional role in supporting the electron transport chain (ETC) complexes and maintaining mitochondrial cristae architecture. In preclinical models of oxidative stress, cardiolipin peroxidation leads to cytochrome c release and downstream apoptotic signalling — a process that SS-31 has been investigated to modulate through cardiolipin stabilisation.
Research indicates that SS-31 does not act as a conventional free-radical scavenger. Instead, it is believed to reduce mitochondrial ROS (reactive oxygen species) generation by preserving the structural integrity of the ETC, thereby limiting electron leak. In preclinical models, SS-31 has been studied for its effects on ATP synthesis efficiency and mitochondrial membrane potential under conditions of cellular stress.
Research Applications
SS-31 has been studied across a wide range of preclinical research models:
- Cardiovascular research: Investigated in ischaemia-reperfusion injury models for its effects on mitochondrial function and cardiomyocyte viability.
- Mitochondrial biology: Used as a tool compound to study cardiolipin-dependent mitochondrial cristae organisation and ETC complex assembly.
- Oxidative stress models: Studied in cellular and rodent models of ROS-mediated damage, exploring mitochondrial ROS attenuation mechanisms.
- Renal research: Investigated in preclinical kidney models examining mitochondrial dysfunction associated with acute injury.
- Neuroscience: Studied in neuronal cell models for mitochondrial protection under conditions of energetic stress.
- Skeletal muscle: Some preclinical work has examined SS-31 in models of muscle mitochondrial dysfunction and age-associated bioenergetic decline.
All listed applications are investigational. Explore the TrueCanPeptides Research Hub →
Storage & Handling
SS-31 should be stored lyophilised at −20°C, protected from light and moisture. Reconstitute with sterile water or appropriate research buffer immediately before use. Due to the peptide’s amphipathic nature, prepare fresh aliquots where possible and avoid extended storage in solution. Protect from freeze-thaw cycling and oxidative conditions.
Full handling notes are available in the TrueCanPeptides Peptide Storage Guide. View quality and purity specifications.
Related Research
Researchers working with mitochondria-targeting compounds may also find these guides relevant:
- SLU-PP-332 — ERR agonist investigated in mitochondrial biogenesis and oxidative metabolism research
- 5-Amino-1MQ — NNMT inhibitor studied in NAD+ metabolism and cellular energy pathways
- Glutathione — master antioxidant tripeptide studied in cellular redox biology
Disclaimer: This content is intended for educational and research purposes only. The compounds discussed on this page are not approved for human therapeutic use by Health Canada or any other regulatory authority. They are not intended to diagnose, treat, cure, or prevent any disease or medical condition. TrueCanPeptides supplies research compounds strictly for in vitro and laboratory research use. All information presented is derived from published preclinical and early-phase research literature and does not constitute medical advice. Consult a qualified healthcare professional before making any health-related decisions.
See also: What is MOTS-c?
SS-31 and Mitochondrial Membrane Research
SS-31 (also known as Elamipretide, MTP-131, or Bendavia) is a synthetic tetrapeptide belonging to the Szeto-Schiller (SS) peptide family — a class of mitochondria-targeting peptides developed by Hazel Szeto at Cornell University. Unlike mitochondria-derived peptides (MDPs) such as MOTS-C, SS peptides are synthetic, designed to penetrate and accumulate in the inner mitochondrial membrane through electrostatic interactions with cardiolipin.
SS-31’s sequence is D-Arg-Dmt-Lys-Phe-NH₂ — a tetrapeptide with alternating aromatic and cationic residues that create a structure capable of interacting with the negatively charged cardiolipin molecules in the inner mitochondrial membrane. Cardiolipin is a unique dimeric phospholipid exclusive to mitochondria and critical for the function and organization of the electron transport chain (ETC) complexes.
Structure and Chemistry
- Sequence: D-Arg-Dmt-Lys-Phe-NH₂ (Dmt = 2′,6′-dimethyltyrosine)
- Amino acids: 4 (tetrapeptide with D-amino acid and non-standard residue)
- Molecular weight: ~640 Da
- Key structural feature: Dmt (dimethyltyrosine) — a modified tyrosine residue with increased antioxidant activity via radical scavenging
- Cell penetration: Freely cell-permeable without carrier due to alternating charge pattern
- Mitochondrial targeting: Inner membrane accumulation via cardiolipin binding — does not require mitochondrial membrane potential for targeting
- Format: Lyophilized powder
Proposed Mechanisms
- Cardiolipin interaction: SS-31 binds cardiolipin and is proposed to restore its proper organization around cytochrome c and ETC complexes, improving electron transport efficiency and reducing electron leak
- Reactive oxygen species (ROS) scavenging: The Dmt residue confers intrinsic antioxidant activity, proposed to neutralize mitochondrial superoxide and hydrogen peroxide at the source
- ATP production: In models of mitochondrial dysfunction, SS-31 has been associated with improved ATP synthesis efficiency — proposed to be secondary to improved ETC complex organization
- Cytochrome c stabilization: Research has suggested SS-31 prevents cardiolipin peroxidation, which can convert cytochrome c from an electron carrier to a peroxidase — a pro-apoptotic conversion
SS-31 vs MOTS-C: Two Approaches to Mitochondrial Research
| Property | SS-31 (Elamipretide) | MOTS-C |
|---|---|---|
| Origin | Synthetic (Szeto-Schiller design) | Mitochondrial genome-encoded |
| Target | Inner mitochondrial membrane / cardiolipin | AMPK pathway / nucleus |
| Mechanism | ETC organization, ROS scavenging | AMPK activation, metabolic gene regulation |
| Size | 4 AA, ~640 Da | 16 AA, ~2,174 Da |
| Clinical development | Phase II/III trials (cardiac/renal) | No clinical trials |
Storage and Handling
- Store lyophilized at −20°C; protect from light and moisture
- Reconstitute in sterile water; water-soluble
- Post-reconstitution: 4°C for up to 7 days; aliquot and freeze at −20°C for longer storage
- Contains Dmt (dimethyltyrosine) — light-sensitive; keep vials covered
SS-31 is supplied for qualified in vitro laboratory research purposes only. Not for human or animal administration. Not evaluated or approved by Health Canada.
Available: SS-31 10mg from TrueCanPeptides | MOTS-C guide | Immune & Longevity research compounds