SS-31 (Elamipretide)

SS-31 (Elamipretide) is a mitochondria-targeted tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that selectively accumulates in the inner mitochondrial membrane — a targeting capability achieved through the peptide's cationic (positively charged) and lipophilic (fat-soluble) properties, which drive its accumulation in the negatively charged, lipid-rich mitochondrial matrix. SS-31's primary mechanism centres on its interaction with cardiolipin — a phospholipid unique to the inner mitochondrial membrane that is essential for the structural organisation of respiratory chain complexes and ATP synthase. In conditions of mitochondrial stress, cardiolipin undergoes peroxidation and remodelling, disrupting the superassembly of respiratory chain complexes (supercomplexes) and impairing oxidative phosphorylation. SS-31 binds cardiolipin with high affinity, stabilising its molecular structure and preventing peroxidation, thereby restoring the organisation of respiratory chain supercomplexes and normalising electron transport efficiency. By stabilising cardiolipin, SS-31 reduces electron leak at complexes I and III — the primary sites of mitochondrial reactive oxygen species (ROS) production — and improves ATP synthesis. The peptide's selective mitochondrial accumulation distinguishes it from non-targeted antioxidants and makes it a unique research tool for studying mitochondrial function, oxidative stress, and organelle-specific signalling in tissue repair and cellular energy metabolism.