Unique mitochondrial targeting
SS-31 contains a Trp-bearing sequence (D-Arg-2,6-dimethyl-Tyr-Lys-Phe) that selectively partitions into the inner mitochondrial membrane. Concentration there is 1000x higher than cytosol.
Mechanism
Binds cardiolipin in the inner mitochondrial membrane, protecting it from oxidative damage. Cardiolipin is essential for electron transport chain function. Protection preserves mitochondrial efficiency.
Clinical development
Multiple Phase 2/3 trials by Stealth BioTherapeutics:
- Heart failure with reduced ejection fraction — mixed results
- Primary mitochondrial myopathy
- Age-related macular degeneration
- Barth syndrome (cardiolipin metabolism disorder)
Current status
Not FDA-approved (as of 2026). Stealth has continued development for orphan mitochondrial indications.
Different from MOTS-c?
Different mechanism entirely. SS-31 protects mitochondrial membrane; MOTS-c is a mitochondrial-derived signaling peptide.