SS-31 in Mitochondrial Research Models

Introduction

SS-31, also called elamipretide, is a mitochondrial peptide studied in laboratory research models. It belongs to the metabolic peptides category on Elivena. This article focuses on mitochondrial localization and cardiolipin interaction in in-vitro and preclinical research. All content is for research use only.

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What Is SS-31?

SS-31 is a synthetic peptide. A peptide is a short chain of amino acids. Amino acids are the building blocks of proteins. Mitochondria are organelles inside cells. They produce most of the cell’s ATP. ATP is the main energy currency of cells.

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Mitochondrial Localization: Peer-Reviewed Evidence

Several peer-reviewed studies describe SS-31 localization to mitochondria in laboratory models. Zhao et al. reported that cell-permeable peptide antioxidants targeted to the inner mitochondrial membrane inhibited mitochondrial swelling and oxidative cell death in experimental models (Zhao et al., 2004). The inner mitochondrial membrane is a folded barrier inside mitochondria. It is important for energy production.

Szeto and Birk reviewed the discovery of compounds that restore mitochondrial plasticity in preclinical research (Szeto & Birk, 2014). Mitochondrial plasticity refers to the ability of mitochondria to change shape and function. Siegel et al. reported that a mitochondrial-targeted peptide improved mitochondrial energetics in skeletal muscle of aged mice (Siegel et al., 2013). Energetics means energy production. These studies support the mitochondrial localization background for SS-31 in research models. They do not describe human use.

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Cardiolipin Interaction: Peer-Reviewed Evidence

Cardiolipin is a phospholipid. A phospholipid is a fat molecule with a phosphate group. Cardiolipin is found mostly in the inner mitochondrial membrane. It helps the membrane keep its shape. It also helps membrane proteins work properly.

Birk et al. reported that SS-31 re-energized ischemic mitochondria by interacting with cardiolipin in experimental models (Birk et al., 2013). Ischemic means lacking blood flow. This study was preclinical. Birk et al. also described targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and oxidative phosphorylation (Birk et al., 2014). Electron transport is the process that helps mitochondria make ATP. Oxidative phosphorylation is the main pathway for ATP production.

Szeto reviewed cardiolipin-protective compounds in preclinical research (Szeto, 2014). The review examined how these compounds may support mitochondrial bioenergetics. Bioenergetics means the study of energy flow in living systems. Allen et al. reported that the cardiolipin-binding peptide elamipretide mitigated fragmentation of mitochondria following contraction-induced injury in a preclinical model (Allen et al., 2020). Fragmentation means breaking into pieces. These findings support the cardiolipin interaction background for SS-31.

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Why Researchers Study Mitochondrial Peptides

Mitochondrial peptides are small protein fragments. They affect mitochondrial processes. Researchers study them in cell cultures and isolated mitochondria. These are in-vitro models. In-vitro means outside a living organism.

Peptides like SS-31 can be synthesized in the laboratory. Synthesis means making a molecule in a controlled way. Researchers use synthetic peptides to test hypotheses about mitochondria. Mitochondria regulate energy, cell death, and metabolism. Metabolism is the set of chemical reactions that keep cells alive.

The Elivena brief recommends linking SS-31 to MOTS-c and NAD+ research once related articles are published [1]. MOTS-c is another mitochondrial peptide. NAD+ is a coenzyme involved in cellular energy. A coenzyme is a molecule that helps enzymes work.

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SS-31 in In-Vitro Models

In-vitro models include cell cultures, isolated mitochondria, and membrane preparations. Researchers add SS-31 to these models to observe effects. Common readouts include membrane potential, ATP production, and oxidative markers. Membrane potential is the voltage difference across a membrane. ATP production is measured to see how well mitochondria make energy. Oxidative markers indicate stress levels in cells.

Zhao et al. used assays for mitochondrial swelling and oxidative cell death in experimental models (Zhao et al., 2004). Birk et al. used ischemic mitochondrial models to study cardiolipin interaction (Birk et al., 2013). These are laboratory research models. They are not human studies.

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Research-Use-Only Compliance

Researchers should handle SS-31 according to institutional guidelines. Store the peptide as recommended on the product page. Use appropriate solvents for reconstitution. Reconstitution means dissolving a dry compound in liquid. Work in a controlled laboratory environment. Personal protective equipment is required. Personal protective equipment includes gloves and goggles.

Concentration-response experiments are common in preclinical research. Concentration-response means testing different concentrations to observe effects. This helps establish a working range in a given model. Researchers should not extrapolate in-vitro findings to humans.

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Conclusion

SS-31 is a mitochondrial peptide studied in cardiolipin and mitochondrial membrane research models. Peer-reviewed studies support its use as a research tool for mitochondrial localization and cardiolipin interaction in preclinical and in-vitro models (Zhao et al., 2004; Birk et al., 2013; Birk et al., 2014; Szeto, 2014; Allen et al., 2020). All information is for laboratory use only.

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Closing Disclaimer

For research use only. This content is provided for in-vitro laboratory research purposes. The compounds discussed are not for human consumption and are not approved by the FDA or EMA to prevent, treat, or cure any condition. Introduction into humans or animals is prohibited by law.

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References

1. Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004;279(33):34682-34690.
2. Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, Seshan SV, Pardee JD, Szeto HH. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24(8):1250-1261.
3. Birk AV, Chao WM, Bracken C, Warren JD, Szeto HH. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and oxidative phosphorylation. Br J Pharmacol. 2014;171(8):2017-2028.
4. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029-2050.
5. Allen ME, Pennington ER, Perry JB, et al. The cardiolipin-binding peptide elamipretide mitigates fragmentation of mitochondria following eccentric contraction-induced injury. J Appl Physiol. 2020;128(6):1532-1543.
6. Szeto HH, Birk AV. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clin Pharmacol Ther. 2014;96(6):672-683.
7. Siegel MP, Kruse SE, Percival JM, et al. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics in skeletal muscle of aged mice. Aging Cell. 2013;12(5):763-771.