SS-31 (Elamipretide)

What 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

1. Szeto HH. “First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics.” Br J Pharmacol, 2014;171:2029–2050.
2. Gibson CM et al. “EMBRACE STEMI study: a Phase IIa trial of elamipretide.” J Am Coll Cardiol, 2016;67(11):1252–1264.