What Is SS-31?
SS-31 (Szeto-Schiller peptide 31), also known by its INN name Elamipretide, is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂. It was developed by Hazel Siew-Har Szeto at Cornell University and is distinguished from most research peptides by its unique mechanism: it selectively concentrates in the inner mitochondrial membrane (IMM) independently of mitochondrial membrane potential, where it binds to cardiolipin.
The inclusion of a dimethyltyrosine (Dmt) residue and D-arginine (D-Arg) in its sequence provides both antioxidant activity (via the phenolic hydroxyl of Dmt) and resistance to proteolytic degradation (via the D-amino acid configuration).
Cardiolipin Binding and IMM Protection
Cardiolipin is a unique phospholipid found almost exclusively in the inner mitochondrial membrane, where it plays structural and functional roles essential to mitochondrial physiology:
- Organises and stabilises the electron transport chain (ETC) supercomplex structure
- Essential for the function of Complex I, III, IV, and ATP synthase
- Forms a high-affinity binding site for cytochrome c
- Required for maintenance of cristae morphology
SS-31 binds cardiolipin with high affinity via electrostatic and hydrophobic interactions. This stabilises cardiolipin-cytochrome c interactions, prevents cristae disruption under stress, reduces superoxide generation from the ETC, and inhibits cardiolipin peroxidation — a critical step in apoptotic cytochrome c release. The net effect is preservation of mitochondrial ATP production capacity under conditions of metabolic stress or injury.
Cardiac Research
The largest body of SS-31 research concerns cardiac protection. Studies in rodent ischaemia-reperfusion (I/R) injury models have demonstrated that SS-31 administered before reperfusion significantly reduces infarct size and preserves left ventricular function. The mechanism involves prevention of mitochondrial permeability transition pore (mPTP) opening during the reperfusion phase — a key driver of reperfusion injury.
Heart failure research using SS-31 has shown improvements in mitochondrial cristae morphology, ATP production, and cardiac mechanical performance in hypertrophic and dilated cardiomyopathy models. A Phase 2 clinical trial (HARP trial) in human heart failure demonstrated improved renal and cardiac function after SS-31 infusion — making it one of the few mitochondria-targeted compounds to have entered human trials.
Skeletal Muscle and Ageing Research
Age-related mitochondrial dysfunction contributes to sarcopenia (muscle loss) and reduced exercise capacity in older individuals. SS-31 research in aged animal models has documented improvements in skeletal muscle mitochondrial morphology, respiratory function, and contractile performance.
Studies in aged mice and rats have shown SS-31 can partially reverse the accumulation of fragmented, dysfunctional mitochondria in skeletal muscle — findings relevant to research on frailty, sarcopenia, and the biology of musculoskeletal ageing.
Reconstitution & Sourcing
RetaLABS SS-31 is supplied as lyophilised powder in 10mg and 50mg vial sizes. Reconstitute with sterile water or bacteriostatic water. Store lyophilised at −20°C and reconstituted solution at 2–8°C for up to 4 weeks. Handle reconstituted solutions with care to avoid oxidation of the Dmt residue.
See the Peptide Reconstitution Guide for full protocol notes. All products are for laboratory research use only. A downloadable PDF reference is also available: SS-31 2026 Researcher's Reference Guide.