SS-31

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BUY2GET1SS31-10

Compliance & Disclaimer

• For Research Use Only
• Not FDA or EMA approved for clinical application
• Evidence is limited to preclinical studies; safety and efficacy in humans remain unestablished.

SS-31 is a synthetic tetrapeptide (sequence: D-Arg-Dmt-Lys-Phe-NH₂) belonging to the Szeto–Schiller peptide family, designed to selectively target mitochondria. Its amphipathic structure enables high affinity for cardiolipin, a phospholipid unique to the inner mitochondrial membrane, positioning SS-31 as a model compound for studying mitochondrial bioenergetics and oxidative stress. [peptidesociety.org], [pnas.org]

Mechanistically, SS-31 binds to cardiolipin and modulates its interaction with cytochrome c, reducing peroxidase activity and preserving electron transport chain (ETC) integrity. This interaction stabilizes mitochondrial cristae architecture, optimizes oxidative phosphorylation, and mitigates reactive oxygen species (ROS) generation under stress conditions. SS-31 also influences mitochondrial membrane electrostatics, which may alter ion distribution and improve calcium handling, contributing to mitochondrial resilience during oxidative or ischemic stress. [pnas.org], [biologyinsights.com] [scholars.uthscsa.edu]

Preclinical studies have demonstrated SS-31’s ability to restore mitochondrial function in models of neurodegeneration, cardiovascular disease, and spinal cord injury, primarily through mechanisms involving cardiolipin stabilization and improved ATP synthesis. Research also highlights its role in reversing mitochondrial fragmentation and enhancing respiratory supercomplex assembly in genetic mitochondrial disorders such as Barth syndrome and DCMA (dilated cardiomyopathy with ataxia). [mdpi.com], [thejournal...entral.com] [frontiersin.org], [nature.com]

These findings position SS-31 as a subject of interest in mitochondrial biology, aging research, and oxidative stress studies, with ongoing investigations into its pharmacodynamics, protein interaction landscape, and potential applications in mitochondrial-targeted therapies. [pnas.org]

Key Peer-Reviewed References

1. Mitchell W. et al. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics. J Biol Chem. 2020. DOI:10.1074/jbc.RA120.013930 [scholars.uthscsa.edu]
2. Chavez J.D. et al. Mitochondrial protein interaction landscape of SS-31. PNAS. 2020. DOI:10.1073/pnas.2002250117 [pnas.org]
3. Ravenscraft B. et al. Mitochondrial Cardiolipin-Targeted Tetrapeptide SS-31 Exerts Neuroprotective Effects in Spinal Cord Injury Models. Int J Mol Sci. 2025;26(7):3327. DOI:10.3390/ijms26073327 [mdpi.com]
4. Machiraju P. et al. SS-31 Peptide Reverses Mitochondrial Fragmentation in DCMA Cardiomyopathy. Front Cardiovasc Med. 2019. DOI:10.3389/fcvm.2019.00167 [frontiersin.org]
5. Russo S. et al. Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice. Sci Rep. 2022. DOI:10.1038/s41598-022-24231-4 [nature.com]