SS-31 or elamipretide or MTP-131 or Szeto-Schiller (SS) peptide
SS-31 has been FDA-approved in 2025 for treating Barth syndrome, a rare mitochondrial disorder, by improving cardiac function and exercise tolerance in affected patients. In clinical trials, SS-31 demonstrates potential to alleviate symptoms of primary mitochondrial diseases, including fatigue and muscle weakness, by enhancing mitochondrial bioenergetics.
Clinical research settings’ benefits:
For patients with heart failure, SS-31 shows promise in reducing cardiac ischemia-reperfusion injury and improving overall heart function through mitochondrial stabilization.
SS-31 may benefit individuals with renal diseases by protecting against kidney ischemia-reperfusion damage, potentially slowing progression of chronic kidney disease.
In neurodegenerative conditions like Alzheimer's and Parkinson's, preclinical and early clinical data suggest SS-31 could mitigate neuronal damage by reducing oxidative stress in mitochondria.
Aging-related frailty may be addressed by SS-31, as studies indicate it improves skeletal muscle function and reduces inflammation in elderly models.
SS-31 holds potential for treating orphan cardiomyopathies, where it supports mitochondrial integrity to enhance cardiac output and patient quality of life. Clinical trials have demonstrated that elamipretide can improve myocardial ischemia-reperfusion injury and reduce complications after cardiac surgery.
For cognitive decline associated with aging, SS-31's ability to restore mitochondrial health may improve brain function and memory in clinical settings. SS-31 not only protects mitochondrial function but also plays a role in regulating the apoptotic process. It promotes cell survival by inhibiting endogenous apoptotic signals and delaying cell apoptosis. This property makes Elamipretide show potential in the study of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease because these diseases are often accompanied by abnormal cell apoptosis.
In models of dry age-related macular degeneration, SS-31 has shown efficacy in preserving retinal function by targeting mitochondrial dysfunction in ocular cells. Slow photoreceptor degeneration by preserving EZ (Ellipsoid Zone) integrity. Improve low-luminance vision and reduce GA (Geographic Atrophy) progression (though not statistically significant in Phase 2 primaries). Mitigate oxidative stress and apoptosis in RPE cells (Retinal Pigment Epithelium Cell), potentially delaying vision loss. Offer neuroprotection without cytotoxicity.
Overall, SS-31's broad therapeutic potential extends to metabolic disorders, where it could enhance energy production and insulin sensitivity by optimizing mitochondrial efficiency.
SS-31, a synthetic tetrapeptide, selectively targets mitochondria by binding to cardiolipin in the inner mitochondrial membrane through hydrophobic interactions with acyl chains and electrostatic interactions with phosphate head groups. This binding concentrates SS-31 in the inner membrane, stabilizing cristae morphology and optimizing the organization of respiratory chain supercomplexes.
SS-31 interacts with subunits of oxidative phosphorylation complexes, such as complex III (QCR2 and QCR6), complex IV (NDUA4), and complex V (ATPA and ATPB), near their cardiolipin-binding sites. These interactions enhance electron transport efficiency and reduce hydrogen peroxide production in mitochondria.
By binding to ADP/ATP translocase (ADT1) in its matrix-open state, SS-31 prevents proton leak through charge repulsion while improving ADP sensitivity and ATP export.
SS-31 also binds to creatine kinase S-type near cardiolipin-binding residues, supporting mitochondrial structural integrity and phosphocreatine energy buffering.
In fatty acid β-oxidation, SS-31 interacts with the trifunctional enzyme subunit ECHA near its active site, potentially rescuing proton leak in deficient models.
For 2-oxoglutarate metabolism, SS-31 binds to isocitrate dehydrogenase at sites that may regulate enzymatic activity and NADPH production via electrostatic effects.
Additional interactions with 2-oxoglutarate dehydrogenase complex subunits and aspartate aminotransferase suggest SS-31 modulates TCA cycle flux and redox homeostasis.
Overall, these molecular interactions reduce reactive oxygen species, improve bioenergetics, and mitigate mitochondrial dysfunction at the protein and membrane level. Research Dosing Protocols: Longevity protocol: 20-day cycle, 10 mg/day, twice per year ; General vitality: 500 mcg/day, 5 days on / 2 days off ; Sleep support (microdosing): 2 × 200 mcg/week ; Macular degeneration: 40 mg/day for 12–48 weeks (ReCLAIM and ReCLAIM-2 studies)
Related research materials:
→ SS-31 (Elamipretide) – Research-Grade Mitochondrial Peptide (20 mg)
→ SS-31 (Elamipretide) – Research-Grade Mitochondrial Peptide (50 mg)
Further reading:
→ NAD⁺, mitochondrial function, and longevity research – in-depth overview