SS-31

Elamipretide (also known as SS-31, MTP-131, and Bendavia) is a mitochondria-targeting tetrapeptide that selectively binds cardiolipin, a lipid found in the inner mitochondrial membrane. ^[1] SS-31 is a member of the Szeto-Schiller (SS) peptides known to selectively target the inner mitochondrial membrane. ^[2] It is a water-soluble, aromatic-cationic tetrapeptide that readily penetrates and transiently localizes to the inner mitochondrial membrane. ^[3]

By binding cardiolipin, elamipretide stabilizes mitochondrial cristae structure, reduces oxidative stress, and enhances adenosine triphosphate (ATP) production. ^[1] By interacting with cardiolipin, SS-31 prevents cardiolipin from converting cytochrome c into a peroxidase while protecting its electron-carrying function, thereby protecting the structure of mitochondrial cristae and promoting oxidative phosphorylation. ^[2] In aging models, cardiolipin-targeted peptides can rejuvenate mitochondrial bioenergetics, remodel mitochondrial cristae structure, and restore organ function during aging. ^[4]

In September 2025, elamipretide was granted accelerated approval in the USA to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg, becoming the first disease-specific treatment approved for Barth syndrome. ^[5] Elamipretide is also under phase III clinical development for the treatment of dry age-related macular degeneration and mitochondrial myopathies. ^[5] In early-phase clinical trials, elamipretide administration has not resulted in any severe adverse events and has shown promising improvements in cardiac hemodynamics at highest doses, but additional studies are necessary to describe its long-term safety and efficacy. ^[6] For patients with primary mitochondrial myopathies, preliminary phase I and II multicenter trials of elamipretide indicated safety and suggested improvement in 6-minute walk test performance and fatigue scales. ^[7]

Mitochondrial dysfunction is centrally involved in the aging process and in an expansive array of disease states, making mitochondria-targeted therapies a topic of scientific and clinical interest. ^[8] SS-31 has been discussed among mitochondrial protective compounds studied for aging and healthspan, alongside the mitochondrial antioxidants MitoQ and SkQ1. ^[9]