Elamipretide (SS-31, MTP-131)

Elamipretide (SS-31, MTP-131) binds with high affinity to cardiolipin, an anionic phospholipid expressed on the inner mitochondrial membrane that is required for cristae formation. In addition, the complex formed with cardiolipin inhibits cytochrome c peroxidase activity, which catalyzes cardiolipin peroxidation and results in mitochondrial damage during ischemia, by protecting its heme iron.^[1]

Intracellular targeting of Elamipretide (SS-31, MTP-131) is determined by incubating feline kidney cells, grown in biotin-free media for 24 hours, with biotinylated SS-31 for 1 hour. Cells are then fixed with 4% paraformaldehyde, permeabilized with 0.1% triton, and treated with Streptavidin-AlexaFluor594 for 30 minutes at room temperature. Fluorescence staining is observed by wide-field fluorescent microscope.

Pretreatment of rats with Elamipretide (SS-31, MTP-131) protects cristae membranes during renal ischemia and prevents mitochondrial swelling. Prompt recovery of ATP on reperfusion leads to rapid repair of ATP-dependent processes, such as restoration of the actin cytoskeleton and cell polarity. Rapid recovery of ATP also inhibits apoptosis, protects tubular barrier function, and mitigates renal dysfunction.^[1]

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