SS-31 (also known as Szeto-Schiller peptide 31, elamipretide, or MTP-131) is a synthetic tetrapeptide developed by Hazel Szeto and Peter Schiller at Weill Cornell Medicine. Its sequence — D-Arg-2′,6′-Dmt-Lys-Phe-NH2 — was designed with a specific architectural goal: to concentrate within the inner mitochondrial membrane via electrostatic and hydrophobic interactions, where it binds to cardiolipin and protects the structural integrity of the electron transport chain.
What Is SS-31?
SS-31 belongs to a class of cell-permeable peptides known as Szeto-Schiller (SS) peptides, designed to selectively target the inner mitochondrial membrane. The alternating aromatic/cationic sequence gives the peptide a net positive charge at physiological pH and an amphipathic character, enabling it to pass through plasma membranes and accumulate in mitochondria at concentrations roughly 1000-fold higher than in the cytoplasm.
The compound received orphan drug designation from the FDA for Barth syndrome (a rare mitochondrial cardiomyopathy), and has been evaluated in Phase II clinical trials for heart failure with preserved ejection fraction (HFpEF) and ischaemia-reperfusion injury — among the few peptides with this depth of clinical investigation specifically targeting mitochondrial function.
Cardiolipin: The Central Target
Cardiolipin is a unique phospholipid found almost exclusively in the inner mitochondrial membrane. It plays a structural role in organising the electron transport chain complexes (particularly Complex I and Complex III) into supercomplexes that maximise electron transfer efficiency. With ageing, oxidative stress, and disease, cardiolipin is progressively oxidised and its structure degrades — disrupting supercomplex organisation, increasing reactive oxygen species (ROS) production, and reducing ATP synthesis efficiency.
SS-31 binds directly to cardiolipin via electrostatic and hydrogen-bonding interactions. Research demonstrates that this binding protects cardiolipin from peroxidation, preserves cristae architecture, maintains supercomplex assembly, and reduces electron leak (and therefore ROS generation) from the ETC. The result, in preclinical models, is restored ATP production in aged or stressed mitochondria.
Research Applications
Mitochondrial Dysfunction in Ageing
Mitochondrial dysfunction is one of the nine Hallmarks of Aging. As cells age, accumulated mtDNA mutations, declining mitochondrial biogenesis (PGC-1α pathway), and cardiolipin oxidation progressively reduce the cell's capacity for aerobic energy production. SS-31 has demonstrated reversal of age-related mitochondrial dysfunction in skeletal muscle, cardiac tissue, and neurons in rodent models, including measurable improvements in exercise capacity and grip strength in aged mice.
Cardiac and Ischaemic Protection
Cardiac cells have the highest mitochondrial density of any tissue and are acutely sensitive to mitochondrial dysfunction. SS-31's clinical development has focused heavily on cardiac applications: reducing infarct size in ischaemia-reperfusion models, improving ejection fraction in heart failure models, and reducing mitochondrial permeability transition pore (mPTP) opening — the catastrophic event that triggers cell death following ischaemic injury.
Neurodegenerative and Metabolic Research
Neurons and metabolically active cells in the liver and kidney are also studied with SS-31, given their high energy demands and vulnerability to mitochondrial dysfunction. Researchers studying neurodegeneration, insulin resistance, and renal injury all use SS-31 as a probe for the contribution of mitochondrial dysfunction to those pathologies.
Research Dosage Protocol
Standard research dosage: 1–3 mg per day via subcutaneous injection
Administration: Subcutaneous injection after reconstitution with bacteriostatic water
Half-life: Relatively short; daily dosing is standard in research protocols
Cycle length: Research protocols typically run 4–12 weeks to assess mitochondrial biomarker changes
Use the BAC Water Calculator to determine exact concentration and IU draw for your SS-31 vial before beginning a protocol.
SS-31 Paired with Epitalon and MOTS-C
For comprehensive longevity research targeting multiple ageing hallmarks simultaneously, SS-31 is frequently studied alongside Epitalon and MOTS-C. Epitalon addresses nuclear longevity pathways (telomere maintenance, gene expression); SS-31 addresses the mitochondrial hallmark (bioenergetics, ROS, cardiolipin integrity); MOTS-C — itself a mitochondria-derived peptide — modulates AMPK and glucose metabolism, improving metabolic flexibility. This three-compound combination covers three distinct cellular ageing mechanisms, making it a high-value research stack for geroscience applications.
Where to Buy SS-31 in India
Peptide Central stocks SS-31 at 99% purity, HPLC-verified with COA included. Pan-India delivery with COD available. SS-31 is stored cold and dispatched with cold protection — important for peptide integrity during Indian summers.
Frequently Asked Questions
How does SS-31 accumulate in mitochondria?
SS-31's alternating aromatic/cationic sequence gives it a net positive charge and amphipathic structure that drives mitochondrial accumulation via the electrochemical gradient across the inner mitochondrial membrane, reaching concentrations approximately 1000-fold higher than cytoplasmic levels.
What is the standard SS-31 research dosage?
Most research protocols use 1–3 mg per day via subcutaneous injection. Dosing in published preclinical studies spans a range from 0.5 to 5 mg/kg, with 1–3 mg/day being the most commonly referenced range in human-scale research contexts.
What is cardiolipin and why does it matter?
Cardiolipin is a phospholipid almost exclusive to the inner mitochondrial membrane that organises electron transport chain complexes into energy-efficient supercomplexes. Age-related cardiolipin oxidation degrades supercomplex architecture, increasing ROS and reducing ATP production. SS-31 binds and protects cardiolipin from peroxidation.
How does SS-31 differ from other antioxidants targeting mitochondria?
Unlike general antioxidants (vitamin E, CoQ10) that act systemically, SS-31 accumulates specifically at the inner mitochondrial membrane where it binds cardiolipin. This precise localisation makes it a more targeted tool for studying mitochondrial ETC function than systemically distributed antioxidants.