SS-31

Molecular Information

Research Summary

SS-31 belongs to the Szeto-Schiller (SS) peptide family, designed to target and accumulate in the inner mitochondrial membrane. The peptide selectively binds to cardiolipin, a phospholipid uniquely present in the inner mitochondrial membrane that is critical for electron transport chain function. Research in animal models has demonstrated protective effects on mitochondrial function in various disease and aging models. Studies have shown that SS-31 can improve mitochondrial bioenergetics, reduce reactive oxygen species production, and preserve mitochondrial cristae structure.

Mechanism of Action

SS-31 concentrates more than 1000-fold in the inner mitochondrial membrane due to its alternating aromatic-cationic structure. It selectively binds to cardiolipin, stabilizing cytochrome c interactions and optimizing electron transport chain function. This reduces electron leak and reactive oxygen species generation at Complex I and Complex III. The peptide does not scavenge ROS directly but rather prevents their overproduction at the source.

Published Animal Studies

• [1]Aged mouse models demonstrated improved mitochondrial function and reversal of age-related bioenergetic decline (Siegel et al., 2013)
• [2]Cardiac ischemia-reperfusion models in rats showed significant cardioprotective effects with reduced infarct size (Szeto et al., 2011)
• [3]Rodent kidney injury models demonstrated renoprotective effects through preservation of mitochondrial function (Birk et al., 2013)
• [4]Aging rodent studies showed improved skeletal muscle function and mitochondrial ATP production capacity (Campbell et al., 2019)

In-Vitro Research

• •Cardiolipin binding assays demonstrated selective high-affinity interaction with the target phospholipid
• •Mitochondrial respiration studies in isolated organelles showed improved respiratory control ratios
• •ROS measurement assays demonstrated reduced superoxide and hydrogen peroxide production from electron transport chain
• •Cytochrome c studies showed stabilization of cardiolipin-cytochrome c interactions

Research Applications

References

1. 1.Szeto HH. "First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics." Br J Pharmacol. 2014;171(8):2029-2050.
2. 2.Siegel MP, et al. "Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice." Aging Cell. 2013;12(5):763-771.