Mitochondria · SS-31
SS-31: a cardiolipin-targeted peptide in mitochondrial research
October 14, 2026 · 1 min read · Models: Mouse, Isolated mitochondria
SS-31 is a cell-permeable tetrapeptide that concentrates at the inner mitochondrial membrane and binds cardiolipin. Studies in isolated mitochondria and in mice have made it a widely used tool for studying mitochondrial bioenergetics and cardiolipin.
A summary of published research for scientific reference. It is not medical advice and does not describe or endorse use in humans or animals. Findings from cell culture and animal models often do not carry over to other systems.
Design
The Szeto–Schiller (SS) peptides alternate aromatic and basic residues (SS-31: D-Arg-dimethylTyr-Lys-Phe-NH₂). This gives a +3 net charge that lets them cross membranes without depending on membrane potential. They accumulate many-fold in the inner mitochondrial membrane, where SS-31 interacts with cardiolipin, a phospholipid essential for cristae structure and electron transport chain supercomplexes.
Findings
Siegel and colleagues (Aging Cell, 2013) measured mitochondrial ATP production and coupling in skeletal muscle of aged mice within hours of receiving the peptide. Other rodent studies have examined oxidative-stress markers in models of cardiac ischemia–reperfusion, heart failure and kidney injury.
In isolated mitochondria and liposome systems, SS-31 limits cardiolipin peroxidation. It also reduces the peroxidase activity of the cytochrome c–cardiolipin complex, an early step in apoptosis.
Considerations
SS-31 is also known as elamipretide. Its mechanism is still being refined: early descriptions emphasized direct ROS scavenging, but more recent work points to membrane and cardiolipin interactions as the main mode of action.
References
- Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029–2050.
- Siegel MP, Kruse SE, Percival JM, et al. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 2013;12(5):763–771.