SS-31 Peptide Structure
SS-31 (also called elamipretide) is a peptide that specifically targets mitochondria, offering a diverse array of therapeutic benefits. Clinical evidence indicates that SS-31 demonstrates promise in addressing numerous medical conditions stemming from mitochondrial dysfunction.
SS-31 Mechanisms of Action
SS-31 operates within cells by selectively aggregating inside the inner mitochondrial membrane, where it binds to cardiolipin, a critical component of mitochondrial structure and function. By binding to cardiolipin, SS-31 helps maintain the shape of the mitochondria’s inner folds, known as cristae, which facilitates their energy-producing capabilities [R].
SS-31 also functions as a potent antioxidant, neutralizing damaging reactive oxygen species (ROS). This action helps to prevent oxidative stress and maintain mitochondrial function [R].
Further, SS-31 promotes the flow of electrons through the mitochondrial respiratory chain, which boosts ATP production – the cell’s energy currency [R].
Lastly, SS-31 has been shown to prevent cell death by inhibiting the activation of pro-apoptotic proteins and preserving mitochondrial integrity [R].
SS-31 and Mitochondrial Dysfunction
Mitochondria are known as “powerhouses” within cells and play a critical role in energy production while maintaining overall cellular homeostasis. When their internal membrane components become compromised, such as cardiolipin, it can result in a cascade of detrimental health effects. SS-31 is a mitochondria-targeting peptide and has shown promising results in addressing mitochondrial dysfunction across various studies.
SS-31 has been found to protect and restore mitochondrial structure, including lengthening mitochondria and restoring cristae membrane structure in kidney disease contexts. It also promotes ATP synthesis, reduces electron leakage, and prevents cardiolipin peroxidation, required for maintaining the inner mitochondrial membrane’s normal structure [R].
In models of mitochondrial cardiomyopathy, SS-31 reversed mitochondrial fragmentation and improved mitochondrial structure and function in patient-derived fibroblasts [R]. SS-31 has also shown promise in improving mitochondrial dysfunction and cognitive impairments in mice models of inflammation-induced cognitive decline [R].
SS-31 and Kidney Disease
SS-31 has demonstrated renoprotective effects, showing promise in treating kidney diseases. It has been found to reduce indicators of inflammation, oxidative stress, and cell proliferation in kidney disease models. Specifically, SS-31 treatment has shown to decrease proteinuria, mesangial expansion, and podocyte deficiency, suggesting its protective effects against renal diseases are significant [R].
SS-31 and Cardiac Dysfunction
In models of cardiac mitochondrial dysfunction, SS-31 has shown beneficial effects by improving mitochondrial structure and function, increasing energy production, and reducing ROS generation. It has been particularly effective in treating cardiomyopathy in Barth Syndrome (BTHS) patients, improving exercise tolerance, muscle strength, and certain cardiac parameters [R].
SS-31, Cancer and Chemotherapy-Induced Cachexia
SS-31 has been effective in ameliorating the whole body energy status in cancer- and chemotherapy-induced cachexia. It partially relieved body weight loss without interfering with tumor growth and improved muscle energetics. Increasing SS-31 dosage was found to be more effective at intermediate time points before the onset of refractory cachexia [R].
SS-31, Oxidative Stress and Autophagy
SS-31 ameliorates oxidative stress by restoring autophagic flux, which protects aged mice from hind limb ischemia. It reduces oxidative stress and improves skeletal muscle structure and function, suggesting it could be a new treatment strategy for peripheral artery disease (PAD) [R].
SS-31 and Diabetes
SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress, and leukocyte-endothelium interactions in type 2 diabetes. It reduces the risk of cardiovascular diseases in T2D patients by improving mitochondrial function and inhibiting mitochondrial permeability transition [R].