SS peptides, compounds that may be able to protect and repair damaged mitochondria


Dysfunctional mitochondria have been implicated in a number of diseases and conditions, ranging from rare genetic disorders to more common ailments such as diabetes and heart disease. Mitochondria are the powerhouses of our cells, generating the energy that our cells need to function properly. When mitochondria become damaged or dysfunctional, they can no longer produce energy efficiently, which can lead to a range of symptoms and health problems.

One group of disorders that is particularly affected by mitochondrial dysfunction is the mitochondrial myopathies, a group of rare genetic disorders that affect the muscles. These disorders are caused by mutations in the genes that encode proteins involved in mitochondrial function. Symptoms can range from mild weakness to severe muscle wasting and respiratory failure, and there is currently no cure for these conditions.

Mitochondrial dysfunction has also been implicated in more common diseases such as diabetes and heart disease. In diabetes, mitochondrial dysfunction has been linked to the development of insulin resistance, a key feature of the disease. In heart disease, mitochondrial dysfunction can lead to reduced energy production in heart muscle cells, which can contribute to the development of heart failure.

Other conditions that may be linked to mitochondrial dysfunction include Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In these conditions, dysfunctional mitochondria may contribute to the death of neurons in the brain, leading to the cognitive and motor symptoms seen in these diseases.

Despite the importance of mitochondrial function in health and disease, there are currently few treatments available for mitochondrial disorders. Some therapies, such as coenzyme Q10 supplementation and mitochondrial-targeted antioxidants, have shown promise in preclinical studies, but more research is needed to determine their efficacy in humans.

Researchers from University of Connecticut led by Professor Nathan Alder are investigating a potential therapy for mitochondrial diseases. The researchers are studying a group of compounds called SS peptides, which protect and even repair damage to mitochondria. SS peptides are made of four amino acids, two of which have a positive charge and two of which are aromatic. They appear to alter and potentially repair mitochondria by changing the electric properties of their membranes.

Mitochondrial membranes are double-layered structures of fatty molecules called lipids that surround proteins sticking out of the membrane. The outer layer of the membrane senses conditions and passes ATP and other molecules back and forth, while the inner layer holds the ATP factories. One of the lipids enriched in the inner membrane is cardiolipin, which has a strong affinity for SS peptides.

Calcium ions can cause damage to mitochondria’s cardiolipin-containing membranes over time, leading to permanent damage. SS peptides can prevent this damage by snuggling up against the mitochondrial membrane and shielding it from calcium ions.

While the researchers have found that SS peptides can alter and protect mitochondria, they are still studying how the peptides interact with mitochondria and why they appear to be effective against so many mitochondrial disorders. The researchers are currently using nuclear magnetic resonance to get detailed pictures of SS peptide structural features and how the peptides might alter or maintain the shape of the mitochondrial membranes. By understanding the mechanism of action, the researchers hope to engineer more effective peptide analogs and tailor them to treat specific mitochondrial afflictions.

In conclusion, dysfunctional mitochondria are a major contributor to a range of diseases and conditions, from rare genetic disorders to more common ailments such as diabetes and heart disease. Further research into the mechanisms of mitochondrial dysfunction and potential therapies is needed to develop effective treatments for these conditions.

SS peptides, compounds that may be able to protect and repair damaged mitochondria. - Medicine Innovates

About the author

Professor  Nathan Alder

Molecular and Cell Biology / Structural Biology, Biochemistry and Biophysics

University of Connecticut

Research Interests: Analysis of the structure, function, and biogenesis of membrane proteins using multiple techniques, primarily fluorescence spectroscopy, and employing yeast as a model system; mitochondrial protein trafficking and assembly; high-resolution fluorescence-based mapping of membrane proteins and analysis of conformational dynamics.


Mitchell W, Ng EA, Tamucci JD, Boyd KJ, Sathappa M, Coscia A, Pan M, Han X, Eddy NA, May ER, Szeto HH, Alder NN. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. J Biol Chem. 2020 May 22;295(21):7452-7469. doi: 10.1074/jbc.RA119.012094.