SS-31 (Elamipretide) Research Overview: Cardiolipin and the Inner Mitochondrial Membrane
Written from the cited peer-reviewed literature; every product lot is third-party tested.
For research purposes only. This content is intended for educational and informational purposes. Products mentioned are sold strictly for laboratory research use. Not for human consumption. Not for human use. Read more
SS-31, also known as elamipretide, is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine. It belongs to the Szeto-Schiller (SS) family of peptides, named after Hazel Szeto and Peter Schiller, who developed them.
SS-31 is studied because it concentrates in mitochondria, specifically the inner mitochondrial membrane. This overview covers its structure, how it reaches mitochondria, its interaction with cardiolipin, and the models it is used in.
Origins
The Szeto-Schiller peptides grew out of research on small synthetic opioid peptides. While studying these compounds, Szeto and Schiller found that some members of the family accumulated in mitochondria. SS-31 became the most studied of them, for its mitochondrial properties and not for opioid receptor activity.
How it reaches mitochondria
SS-31 alternates aromatic residues (Dmt and Phe) with positively charged ones (D-Arg and Lys). This pattern lets it cross cell membranes even though it carries a net positive charge, which normally keeps peptides outside cells. Once inside, it concentrates in the inner mitochondrial membrane.
The D-arginine at the start of the chain makes it resistant to the enzymes that break down natural peptides, and the amidated C-terminus adds further stability.
Cardiolipin
Inside mitochondria, SS-31 binds cardiolipin, a phospholipid found almost exclusively in the inner mitochondrial membrane. Cardiolipin helps organize the protein complexes of the electron transport chain and shapes the folded membranes known as cristae.
A 2014 review by Szeto in the British Journal of Pharmacology summarizes the research on SS-31 and cardiolipin, including laboratory studies of membrane structure, electron transport chain function and the production of reactive oxygen species.
Laboratory models
- Isolated mitochondria: measurements of electron transport, membrane potential and ATP production.
- Cell culture: studies of mitochondrial structure and reactive oxygen species under conditions of cellular stress.
- Animal models: SS-31 has been examined in rodent models involving tissues with high energy demand, such as heart, kidney and skeletal muscle.
Results in isolated mitochondria or one animal model do not establish activity in other systems.
Handling in the laboratory
SS-31 is supplied as a lyophilized powder and is generally reconstituted with bacteriostatic water before use. Sealed vials are stored at -20°C, protected from light and moisture.
Testing and documentation
Every lot we sell is tested by Freedom Diagnostics, an independent laboratory, using HPLC for purity and mass spectrometry for identity. Certificates are published in our COA library, and each can be verified directly with the lab using the search code printed on it. Our guide explains how to verify a COA.
References
- Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology. 2014. pubmed.ncbi.nlm.nih.gov/24117165/
Every lot is third-party tested. View the certificate for SS-31 →
Related reading
For research purposes only. All products from Canada Research Labs are supplied strictly as reference materials for in-vitro laboratory research by qualified professionals. They are not drugs, natural health products or cosmetics, and have not been authorized by Health Canada for any human or veterinary use.
