SS-31

Research Applications:

1. Mitochondrial Membrane Stabilization

SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH₂) is a synthetic peptide engineered to selectively target and bind cardiolipin, a phospholipid unique to the inner mitochondrial membrane. Cardiolipin is critical for the structural organization of mitochondrial respiratory chain complexes. SS-31 stabilizes cardiolipin-rich domains, thereby preserving mitochondrial membrane potential and improving electron flow efficiency [1].

This targeted mechanism makes SS-31 a valuable research tool for investigating mitochondrial membrane dynamics and bioenergetic stability under stress conditions.

2. Reduction of Mitochondrial ROS and Oxidative Damage

One of SS-31’s defining features is its ability to reduce mitochondrial reactive oxygen species (ROS) production without impairing respiration. In cellular and rodent models, SS-31 attenuated superoxide production from complex I and III, leading to lower oxidative stress markers such as 4-HNE and nitrotyrosine [2].

SS-31 is commonly used in oxidative stress research, neurodegeneration models, and studies on redox signaling pathways within mitochondria.

3. Bioenergetic Enhancement and ATP Production

SS-31 improves ATP synthesis efficiency by reducing proton leak and enhancing the coupling of electron transport to oxidative phosphorylation. Studies in aged and metabolically impaired models have shown improved mitochondrial respiration, increased ATP availability, and enhanced cellular energy status following SS-31 administration [3].

These features support its use in energy metabolism studies, especially in skeletal muscle, cardiac tissue, and neurons.

4. Cell Survival and Apoptosis Pathways

By stabilizing mitochondrial membranes and reducing ROS, SS-31 has been observed to attenuate mitochondria-mediated apoptosis in various stress models, including ischemia-reperfusion and neurotoxicity assays. It inhibits the release of cytochrome c and other pro-apoptotic factors, thus supporting research on mitochondrial-driven cell death pathways [4].

Researchers also use SS-31 in models of cardiac injury, organ preservation, and age-related mitochondrial dysfunction.

Referenced Citations

1. Szeto HH, et al. “Cardiolipin-targeted peptides and mitochondrial protection.” PubMed
   Source: Archives of Biochemistry and Biophysics – Binding of SS-31 to cardiolipin.
   
2. Birk AV, et al. “SS-31 reduces mitochondrial oxidative stress.” PubMed
   Source: FASEB Journal – ROS inhibition without impairing respiration.
   
3. Siegel MP, et al. “Improvement of mitochondrial function in aged mice.” PubMed
   Source: Aging Cell – ATP production and energy metabolism.
   
4. Zhao K, et al. “SS-31 in mitochondrial apoptosis suppression.” PubMed
   Source: Journal of Biological Chemistry – Cell survival mechanisms.

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