SS‑31 (elamipretide) is a cell‑permeable tetrapeptide with a unique mechanism of action targeting mitochondrial dysfunction[1]. The peptide selectively accumulates in the inner mitochondrial membrane where it binds to cardiolipin, a specialized phospholipid essential for organizing electron transport chain supercomplexes and maintaining cristae structure[2][7]. By stabilizing cardiolipin‑protein interactions, SS‑31 optimizes electron transport efficiency, reduces pathological reactive oxygen species generation, and enhances ATP synthesis in metabolically active tissues[8]. Preclinical research demonstrated that SS‑31 protects against mitochondrial dysfunction across multiple disease models including heart failure, ischemia‑reperfusion injury, neurodegeneration, chronic kidney disease, and age‑related muscle atrophy[9]. In human clinical trials, SS‑31 showed favorable safety and tolerability profiles with no dose‑limiting toxicities[4][5]. While Phase II trials in heart failure and primary mitochondrial myopathy did not meet primary efficacy endpoints, the TAZPOWER trial in Barth syndrome demonstrated significant improvements in muscle strength and six‑minute walk distance, leading to FDA accelerated approval in 2025[3][10].
