What is SS-31 (Elamipretide)?
SS-31 (elamipretide) is a mitochondria-targeted tetrapeptide studied for its interaction with cardiolipin and the inner mitochondrial membrane. This page summarises the research literature, including cell, animal and cli
SS-31, formally known as elamipretide, is a synthetic mitochondria-targeted tetrapeptide. It is also referred to in the literature as MTP-131, Bendavia, and by the developmental code SS-31. The molecule is a short sequence of four amino acids with alternating cationic and aromatic residues, a structural motif associated with binding to the mitochondrial inner membrane and with reduction of oxidative stress [2]. The evidence block for this page does not supply a full sequence string, molecular formula, or molecular weight, so those identifiers are not stated here.
The research literature on this compound centres on the mitochondrial inner membrane, and specifically on the interaction between the peptide and cardiolipin, a phospholipid that is enriched in that membrane and that participates in the organisation of the electron transport chain. Work in this area treats the peptide as a tool for probing membrane lipid environments and the downstream consequences of membrane perturbation.
Research Studies
SS-31 and radiation-induced senescence in cardiomyocyte models
A study examined the effect of the mitochondrial-targeted peptide on radiation-induced cell senescence in two cell systems: cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) [1]. Exposure to gamma-radiation at doses of 2, 5, and 10 Gy inhibited H9C2 cell proliferation in a dose-dependent manner and induced senescence-associated beta-galactosidase (SA-beta-gal) staining, described in the paper as a gold-standard marker of senescence [1]. The study evaluated whether SS-31 attenuated this radiation-induced senescence phenotype in those cell models [1]. This is in vitro work; the findings were observed in cultured cardiomyoblast and stem-cell-derived cardiomyocyte populations, not in whole animals or in humans.
SS-31 and alpha-synuclein membrane binding and aggregation
Membrane binding and aggregation properties of alpha-synuclein are closely associated with Parkinson's disease and a class of related syndromes termed synucleinopathies [2]. A study explored whether SS-31 could modulate the interaction of alpha-synuclein with lipid membranes and mitigate the impairment of mitochondrial function induced by alpha-synuclein oligomers [2]. Using fluorescence correlation spectroscopy and fluorescence anisotropy, the work demonstrated that SS-31 displaces both wild-type and N-terminally acetylated forms of the protein [2]. The experiments were biophysical and cell-based; the observations concern membrane interaction and oligomer-induced mitochondrial impairment in those systems.
SS-31 and mitochondrial function in synucleinopathy models
The same study reported that SS-31 restored impaired mitochondrial function in the context of alpha-synuclein oligomer exposure [2]. The peptide's known properties of mitochondrial inner membrane binding and oxidative stress reduction were the rationale for testing it against oligomer-induced mitochondrial impairment [2]. As above, this evidence comes from in vitro biophysical and cellular assays rather than from animal or human studies.
Elamipretide in Friedreich Ataxia: an investigator-initiated clinical study
A registered investigator-initiated study was designed to evaluate the safety, tolerability, and activity of elamipretide in treating vision loss in Friedreich Ataxia (FRDA) [3]. The stated objective of the trial record is the evaluation of those three parameters in that specific population [3]. This is a clinical study record; it is the only human-study entry in the evidence set for this page, and it addresses a defined patient group with a defined outcome measure.
SS-31 and MitoQ in aged female mice under nutritional stress
A comparative study evaluated mitochondria-targeted compounds, specifically MitoQ and SS-31 (elamipretide), in aged female mice under nutritional stress, in the context of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) [4]. The paper frames MASLD as a major cause of cirrhosis, liver cancer, and cardiovascular disease, and notes that early mitochondrial dysfunction drives lipid imbalance, inflammation, and fibrosis [4]. It further notes the absence of approved pharmacological treatments for the condition, which is the stated rationale for comparing mitochondria-targeted approaches [4]. The findings were observed in aged female mice; they are animal data.
Peptide therapies in musculoskeletal injury and athletic performance
A review examined the safety and efficacy of approved and unapproved peptide therapies for musculoskeletal injuries and athletic performance [5]. It describes peptides as short amino acid chains occupying a pharmacological niche between small-molecule drugs and large proteins, and notes that their use in sports medicine is expanding, driven by patient demand for accelerated injury recovery and performance enhancement [5]. The review also notes that numerous peptide drugs have undergone rigorous assessment [5]. This source is included as context on the broader peptide-therapeutics landscape rather than as a study of SS-31 specifically.
Comparison of evidence types across the SS-31 literature
The table below summarises the model systems and evidence categories represented in the sources cited on this page. It is intended to make clear which findings are cell-based, which are animal-based, and which come from a registered human study.
| Source | Model or population | Evidence category |
|---|---|---|
| [1] | H9C2 cardiomyoblasts; hiPSC-CMs | In vitro |
| [2] | Lipid membrane systems; alpha-synuclein oligomer assays | In vitro / biophysical |
| [3] | Friedreich Ataxia patients (registered study) | Clinical study record |
| [4] | Aged female mice under nutritional stress | Animal |
| [5] | Review of peptide therapies in sports medicine | Review |
What the evidence does not establish
Across the sources cited here, the mechanistic findings for SS-31 come predominantly from cultured cells and biophysical membrane systems [1][2], with one comparative animal study in aged female mice [4] and one registered clinical study record in a specific patient population [3]. No source in this evidence set provides a human dose, a dosing schedule, or a clinical efficacy conclusion for general use. Claims about outcomes in humans are not supported by the material available here and are therefore not made on this page.
If you are reading this for personal health reasons
This material is sold for laboratory research only, and we do not provide dosing or medical guidance. Anyone considering a compound for themselves should speak to a licensed clinician. Nothing on this page is medical advice or a recommendation for personal use.
Sources
- [1] Mitochondrial-targeted SS-31 peptide attenuates radiation-induced cardiomyocyte senescence. https://europepmc.org/article/PMC/PMC13400571
- [2] Therapeutic Peptide SS-31 Modulates Membrane Binding and Aggregation of alpha-Synuclein and Restores Impaired Mitochondrial Function. https://pubmed.ncbi.nlm.nih.gov/42219795/
- [3] FRDA Investigator Initiated Study (IIS) With Elamipretide. https://clinicaltrials.gov/study/NCT05168774
- [4] Targeting Mitochondria in MASLD: Comparative Evaluation of MitoQ and SS-31 (Elamipretide) in Aged Female Mice under Nutritional Stress. https://pubmed.ncbi.nlm.nih.gov/42708867/
- [5] Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance. https://pubmed.ncbi.nlm.nih.gov/41966639/