SS-31 (Elamipretide): Cardiolipin Targeting and the Mitochondrial Literature

Evidence at a glance

Human trials, investigational

Elamipretide has been through several registered human trials in rare mitochondrial disease, with mixed results across the programme.

Why researchers are interested

It concentrates in the inner mitochondrial membrane and binds cardiolipin, the lipid that holds the cristae in shape. Stabilising that structure is a direct attempt to restore ATP production at its source rather than to compensate for the loss further downstream.

What the research found

• Better mitochondrial functionCardiolipin binding shown to stabilise cristae structure and support ATP production
• Improved walking distanceGains in six minute walk distance in earlier primary mitochondrial myopathy trials
• Barth syndrome signalImprovement reported over the extension phase of its Barth syndrome trial

Reported in the literature

• Injection site reactions were the most commonly reported effect across trials.
• Results across the programme have been mixed. Later trials did not all repeat the earlier gains.
• Trials were run in defined rare disease populations, not in healthy adults.
• Not approved as a general purpose compound.

Findings are summarised from the sources listed under References on this page, and from approved product labelling where a compound has one. These are outcomes observed in published studies, not effects claimed for any person, and nothing here is a recommendation for human use.

← All research guides

SS-31 (elamipretide) is a four-residue peptide that reaches the inner mitochondrial membrane by a route most mitochondria-targeted compounds cannot use. That mechanism is what makes it distinctive, and it is the part worth understanding before reading any of its results. This guide covers identity, how the targeting works, what the published literature examined, and how the material is handled. It is written for researchers and is not medical guidance.

What SS-31 is

• Names SS-31, elamipretide, MTP-131, Bendavia
• CAS 736992-21-5 (PubChem CID 11764719)
• Molecular formula C₃₂H₄₉N₉O₅
• Molar mass 639.8 g/mol
• Sequence D-Arg-Dmt-Lys-Phe-NH₂

Verified against PubChem on 2 October 2026. It belongs to the Szeto-Schiller family, which is where the “SS” designation comes from; the number is its position in that series. At four residues it is one of the smallest compounds in this catalogue — roughly a seventh the mass of tesamorelin.

Research-use note: SS-31 is a research chemical supplied strictly for laboratory research. It is not an approved drug, cosmetic, or supplement and is not for human or animal consumption. Findings below come from cell-culture and animal-model work.

The targeting mechanism, and why it is unusual

Getting a molecule into mitochondria is the hard part of mitochondrial pharmacology, and there are broadly two ways to do it.

The conventional route depends on membrane potential. Compounds conjugated to a lipophilic cation — TPP-tagged molecules being the familiar example — accumulate because the inner membrane carries a strong negative potential that drags them in. The catch is circular: the compounds that most need studying are often those in damaged mitochondria, and damaged mitochondria have a collapsed membrane potential. Exactly where you want the compound, it accumulates least.

SS-31 does not work that way. Its alternating aromatic-cationic motif allows it to concentrate in the inner mitochondrial membrane independently of membrane potential. That is the property that made the Szeto-Schiller series interesting, because it does not fail in the condition it is meant to study.

Once there, published work has examined its association with cardiolipin, a phospholipid concentrated in the cristae folds of the inner membrane, with reported downstream effects on cristae architecture, electron-transport efficiency and reactive-oxygen-species generation in laboratory models.

What the published literature covers

• Zhao et al. (J Biol Chem, 2004) — characterised cell-permeable peptide antioxidants targeted to the inner mitochondrial membrane, reporting effects on mitochondrial swelling and oxidative cell death. This is the foundational paper for the series.
• Birk et al. (J Am Soc Nephrol, 2013) — reported that SS-31 re-energised ischemic mitochondria through its interaction with cardiolipin, which is the work that moved the mechanism from “antioxidant” to “cardiolipin-interacting”.
• Szeto (Br J Pharmacol, 2014) — reviewed cardiolipin-protective compounds and the restoration of mitochondrial bioenergetics.

Worth noting how the framing shifted across those three. The early work described SS-31 as an antioxidant; the later work reframed it as acting through cardiolipin binding and cristae structure, with reduced ROS as a consequence rather than the mechanism. Citing the 2004 description as though it were the current understanding is a common error.

These findings describe outcomes in laboratory models, not validated outcomes in humans.

Where it sits among the mitochondrial compounds

Three compounds in this catalogue touch mitochondrial research from different directions, and they are not substitutes:

• SS-31 — targets the inner membrane itself, via cardiolipin and cristae structure.
• MOTS-c — a peptide encoded by the mitochondrial genome, studied in metabolic signalling.
• NAD+ — the coenzyme carrying electrons through the respiratory chain.

Structure, signalling and cofactor supply respectively. A study picking among them should pick on which of those three it is actually about.

Form, reconstitution and storage

Supplied as a lyophilized powder. Standard laboratory practice is to reconstitute with bacteriostatic water, swirl rather than shake until dissolved, and store the reconstituted solution refrigerated at 2–8 °C. The sealed vial is kept frozen and protected from light, and repeated freeze-thaw cycles are avoided. See how to reconstitute peptides.

(General lab-handling notes, not usage instructions.)

For research use only

All products and information referenced here are intended strictly for laboratory and scientific research use only. They are not for human or animal consumption and are not drugs, foods, supplements, or medical devices. Nothing here should be interpreted as medical advice, and no outcome in a person is described, implied or promised. Products are supplied against a stated purity specification.

Explore SS-31 and related research compounds

• SS-31 — specifications and stated purity
• MOTS-c — mitochondrial-derived peptide
• NAD+ — redox coenzyme
• Full research catalog

Common questions about SS-31

Is SS-31 the same as elamipretide?

Yes. SS-31, elamipretide and MTP-131 are names for the same tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2.

What does "SS" stand for?

Szeto-Schiller, after the researchers who developed this family of aromatic-cationic peptides.

How is SS-31 different from MOTS-c?

SS-31 is a synthetic peptide that concentrates in the inner mitochondrial membrane and is studied for its interaction with cardiolipin. MOTS-c is encoded by mitochondrial DNA itself and is studied as a metabolic signaling peptide.

References

1. Zhao K, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004. PubMed
2. Birk AV, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013. PubMed
3. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014. PubMed
4. Compound identity verified against the PubChem database, retrieved 2 October 2026. PubChem