SS-31 (Elamipretide): How a Mitochondria-Targeted Peptide Works

SS-31 — also called elamipretide, MTP-131 or Bendavia — is one of the few peptides designed specifically to reach the inside of mitochondria. That makes it a reference compound in mitochondrial-dysfunction research.

What SS-31 is

SS-31 is a synthetic tetrapeptide: D-Arg–dimethylTyr–Lys–Phe-NH₂. It belongs to the Szeto–Schiller (SS) family of aromatic-cationic peptides. Its alternating positive charges and aromatic rings let it cross cell membranes and concentrate in the inner mitochondrial membrane, independently of membrane potential.

Elamipretide has been through clinical trials for mitochondrial disorders, with mixed results across indications. It is not licensed in the UK. Research material is for laboratory use only.

How it is thought to work

The leading explanation centres on cardiolipin, a phospholipid found almost only in the inner mitochondrial membrane:

1. Cardiolipin binding. SS-31 binds cardiolipin through electrostatic and hydrophobic interactions.
2. Cristae structure. That binding is thought to stabilise the folded inner membrane (cristae) where energy production happens.
3. Electron transport. Keeping cardiolipin in place helps electron-transport-chain supercomplexes work efficiently and reduces electron leak.
4. Less oxidative stress. Less electron leak means fewer reactive oxygen species (ROS), which protects cardiolipin from peroxidation — a feedback loop that can otherwise damage mitochondria.

Earlier work described SS-31 mainly as an antioxidant. The cardiolipin-centred model is now more widely cited.

What the research looks at

• Cardiac ischaemia–reperfusion and heart-failure models
• Skeletal muscle ageing and mitochondrial function in rodents
• Kidney injury models
• Rare inherited mitochondrial disease (in the clinical programme)

Related compounds

MOTS-c and NAD+ are studied in the same field through quite different mechanisms.

Comparing SS-31 listings

1. Confirm the D-arginine and dimethyltyrosine are specified. These non-standard residues are essential to the molecule's activity.
2. Check that the mass-spec result matches about 640 Da (free base; salt forms will differ).
3. Compare price per mg on our SS-31 comparison page.

Summary

SS-31 is a mitochondria-targeted tetrapeptide whose main proposed action is stabilising cardiolipin and the electron transport chain. PeptideCompare provides no dosing or usage guidance, and nothing here is for human or veterinary use.