SS-31
Also known as: Elamipretide, MTP-131, Bendavia
SS-31 (elamipretide) is a mitochondria-targeted tetrapeptide that concentrates in the inner mitochondrial membrane, where it interacts with cardiolipin to protect cristae structure, reduce ROS production, and improve bioenergetic efficiency.
Sequence
D-Arg-Dmt-Lys-Phe-NH2 (tetrapeptide)
Molecular Weight
639.8 Da
Target
Cardiolipin (inner mitochondrial membrane)
Mitochondrial Accumulation
~1,000× enrichment in IMM
Clinical Stage
Phase II/III completed (heart failure, MMPOWER)
Research Use Only
Not for human or veterinary use
Overview
SS-31 (also designated elamipretide, MTP-131, or Bendavia) is a synthetic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that belongs to the Szeto-Schiller family of mitochondria-targeted peptides, developed by Hazel Szeto at Cornell University and Richard Schiller. The peptide's alternating aromatic and basic amino acids confer both cell permeability and a remarkable affinity for the inner mitochondrial membrane (IMM), where it concentrates to concentrations estimated at 1,000-fold over cytoplasmic levels despite its positive charge.
The primary molecular target of SS-31 is cardiolipin, a unique phospholipid found almost exclusively in the IMM where it plays critical structural and functional roles. Cardiolipin is essential for the assembly and stability of the electron transport chain (ETC) supercomplexes and is required for optimal cytochrome c binding during oxidative phosphorylation. Oxidative damage to cardiolipin — a common consequence of mitochondrial ROS overproduction — disrupts ETC supercomplex architecture and impairs ATP synthesis efficiency. SS-31 protects cardiolipin from peroxidation through electron transfer activity and physical stabilization of cristae membrane structure.
Research applications of SS-31 span multiple disease models. In ischemia-reperfusion injury models (cardiac, renal, cerebral), SS-31 administration has consistently reduced infarct size, preserved mitochondrial morphology, and improved functional recovery. Studies in heart failure models have documented improvements in left ventricular function associated with enhanced mitochondrial cristae density and ETC efficiency. In aged animal models, SS-31 has been shown to reverse age-related declines in skeletal muscle mitochondrial function, ATP production, and exercise capacity.
SS-31 advanced to Phase II and Phase III clinical trials for several indications including heart failure and mitochondrial myopathy (MMPOWER study), making it one of the most clinically developed mitochondria-targeted peptides. Investigators have access to both extensive preclinical mechanistic data and clinical pharmacology information. SS-31 is available for research use only.
Mechanism of Action
SS-31 binds cardiolipin through electrostatic interaction with its positively charged lysine and arginine residues combined with hydrophobic interaction via the dimethyltyrosine (Dmt) residue. This dual interaction positions SS-31 within the cardiolipin bilayer where it acts as an electron shuttle to reduce ROS generation at Complex I and III of the ETC. By minimizing cardiolipin oxidation, SS-31 preserves the structural integrity of ETC supercomplexes (respirasomes), maintaining electron transfer efficiency.
Downstream effects include normalization of mitochondrial membrane potential (ΔΨm), reduced cytochrome c release (and thus reduced apoptotic signaling), restored calcium buffering capacity, and improved cristae morphology as measured by electron microscopy. In aging research, SS-31 restores the ratio of fused to fragmented mitochondria, consistent with effects on mitochondrial dynamics in addition to bioenergetics.
Research Applications
- Mitochondrial cardiolipin biology and inner membrane research
- Ischemia-reperfusion injury models (cardiac, renal, cerebral)
- Aging-related mitochondrial dysfunction and bioenergetics
- Electron transport chain supercomplex stability studies
- Heart failure and cardiomyopathy models
- Mitochondria-targeted drug delivery mechanism research
Research Use Only. SS-31 is available for laboratory and research applications only. It is not approved by the FDA or any equivalent regulatory authority for human or veterinary therapeutic use. All information on this page is derived from published preclinical literature and is presented for informational and research context purposes only. Investigators should consult current primary literature and comply with applicable regulations before initiating research.
Order SS-31 for Research →Peptide Family
Mitochondrial Peptides & Metabolic Compounds
Bioenergetics · AMPK · Sirtuin Activation · Cardiolipin
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