SS-31 (Elamipretide): A Mitochondria-Targeted Tetrapeptide
How a four-residue peptide concentrates in the inner mitochondrial membrane, and where it is used in bioenergetics research.
SS-31, also known as elamipretide and MTP-131, is a synthetic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine) from the Szeto-Schiller family of aromatic-cationic peptides, developed by Hazel Szeto's group at Weill Cornell Medical College.
Mechanism overview
The alternating aromatic and cationic residues let SS-31 cross cell membranes without a dedicated transporter and concentrate in the inner mitochondrial membrane. There it binds cardiolipin, a phospholipid that organises the respiratory-chain supercomplexes. Binding is reported to stabilise cristae structure, support electron-transfer efficiency, and reduce excess reactive-oxygen-species production.
Published research applications
SS-31 is used in ischaemia-reperfusion models of heart and kidney, skeletal-muscle ageing models, heart-failure studies, retinal-degeneration work, and models of primary mitochondrial dysfunction. Elamipretide has also been evaluated in clinical studies, including in Barth syndrome, a disorder of cardiolipin remodelling.
Because the compound targets a structural lipid of the mitochondrial membrane rather than a single receptor, it is a common tool for asking whether a phenotype is driven by mitochondrial membrane integrity.
Limits of the evidence
Benefits seen in animal models do not predict outcomes elsewhere, and clinical-trial results have varied across indications. Protocols should include appropriate vehicle controls and mitochondrial readouts specific to the model.
Reconstitution and handling
QSC supplies SS-31 as lyophilized powder in 10-vial packs of 5 mg, 10 mg, and 50 mg vials. Reconstitute in sterile water per your protocol and refrigerate; aliquot to avoid repeated freeze-thaw cycles and keep long-term stock at -20°C as lyophilized powder.
