🧬SS-31 (Elamipretide)
Szeto-Schiller tetrapeptide. Targets cardiolipin on the inner mitochondrial membrane. Restores mitochondrial cristae architecture, reduces ROS, and dramatically improves ETC function. In clinical trials for HFrEF and Barth syndrome.
D-Arg-2'6'-dimethyl-Tyr-Lys-Phe-NH₂What Is SS-31?
SS-31 (elamipretide, MTP-131) is a synthetic tetrapeptide developed by Hazel Szeto and Peter Schiller at Weill Cornell Medicine. It selectively concentrates in the inner mitochondrial membrane (IMM) where it binds cardiolipin — a unique phospholipid essential for cristae architecture and cytochrome c function.
Key Mechanisms
- Cardiolipin interaction — stabilises cardiolipin-cytochrome c complex; prevents cytochrome c release and apoptosis
- Cristae remodelling — restores collapsed cristae architecture in aged/diseased mitochondria
- ETC efficiency — improves electron flux through Complexes I, II, III, IV; reduces proton leak
- ROS reduction — reduces mitochondrial superoxide and H₂O₂ production by 70–90% in models
- ATP production — restores near-normal ATP synthesis rates in mitochondrial dysfunction models
Key References
- Szeto HH. "First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics." Br J Pharmacol, 2014;171:2029–2050.
- Gibson CM et al. "EMBRACE STEMI study: a Phase IIa trial of elamipretide." J Am Coll Cardiol, 2016;67(11):1252–1264.
Frequently Asked Questions
Rather than mopping up reactive oxygen species after the fact like a general antioxidant, SS-31 selectively binds cardiolipin in the inner mitochondrial membrane and stabilises the structure that produces less ROS in the first place — a structural/preventive mechanism rather than a scavenging one.
Clinical trials have investigated it in heart failure with reduced ejection fraction (HFrEF), Barth syndrome, and primary mitochondrial myopathy, reflecting its core mitochondrial-bioenergetics mechanism.
Cardiolipin anchors cytochrome c to the inner mitochondrial membrane; when it's damaged or peroxidised, cytochrome c is released, triggering apoptosis. Stabilising cardiolipin is why SS-31 shows protective effects across cardiac, renal, and skeletal muscle mitochondrial research models.