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Study · In vitro (cell-free) · 2020

6 results

The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action.

Mitchell W, Ng EA, Tamucci JD, Boyd KJ, Sathappa M, Coscia A, Pan M, Han X, Eddy NA, May ER, Szeto HH, Alder NN

The Journal of biological chemistry9 Apr 2020Cited by 114 (Europe PMC)

PMID32273339 (opens in a new tab)PMCIDPMC7247319 (opens in a new tab)DOI10.1074/jbc.ra119.012094 (opens in a new tab)PepBankPUB-32273339
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Summary

Mitochondrial dysfunction underlies many heritable diseases, acquired pathologies, and aging-related declines in health. Szeto-Schiller (SS) peptides comprise a class of amphipathic tetrapeptides that are efficacious toward a wide array of mitochondrial disorders and are believed to target mitochondrial membranes because they are enriched in the anionic phospholipid cardiolipin (CL). However, little is known regarding how SS peptides interact with or alter the physical properties of lipid bilayers. In this study, using biophysical and computational approaches, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitochondrial membranes. Our results show that this polybasic peptide partitions into the membrane interfacial region with an affinity and a lipid binding density that are directly related to surface charge. We found that SS-31 binding does not destabilize lamellar bilayers even at the highest binding concentrations; however, it did cause saturable alterations in lipid packing. Most notably, SS-31 modulated the surface electrostatics of both model and mitochondrial membranes. We propose nonexclusive mechanisms by which the tuning of surface charge could underpin the mitoprotective properties of SS-31, including alteration of the distribution of ions and basic proteins at the interface, and/or modulation of bilayer physical properties. As a proof of concept, we show that SS-31 alters divalent cation (calcium) distribution within the interfacial region and reduces the energetic burden of calcium stress in mitochondria. The mechanistic details of SS-31 revealed in this study will help inform the development of future compound variants with enhanced efficacy and bioavailability.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cell-free)Activity measurement

    SS‑31 partitioned into the membrane interfacial region, with affinity and lipid binding density directly related to surface charge.

    In plain wordsIn lab tests, SS‑31 entered the membrane surface region, and more strongly when the membrane charge was higher.

    Peptide
    Elamipretide (SS-31)
    Outcome
    Not applicableMembrane partitioning and binding
    Study

    n: not reported in source

    model lipid bilayers and mitochondrial membranes
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Our results show that this polybasic peptide partitions into the membrane interfacial region with an affinity and a lipid binding density that are directly related to surface charge.
    1 context sentence
    Summary · context
    In this study, using biophysical and computational approaches, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitochondrial membranes.
  2. 02LabIn vitro (cell-free)Activity measurement

    SS‑31 binding did not destabilize lamellar bilayers even at the highest binding concentrations.

    In plain wordsIn lab tests, SS‑31 did not destabilize layered lipid membranes, even at the highest binding levels.

    Peptide
    Elamipretide (SS-31)
    Outcome
    No significant changeDestabilization of lamellar bilayers
    Study

    n: not reported in source

    model lipid bilayers and mitochondrial membranes
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We found that SS-31 binding does not destabilize lamellar bilayers even at the highest binding concentrations
    1 context sentence
    Summary · context
    In this study, using biophysical and computational approaches, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitochondrial membranes.
  3. 03LabIn vitro (cell-free)Activity measurement

    SS‑31 caused saturable alterations in lipid packing.

    In plain wordsIn lab tests, SS‑31 changed how tightly lipids pack in membranes, up to a limit.

    Peptide
    Elamipretide (SS-31)
    Outcome
    MixedLipid packing
    Study

    n: not reported in source

    model lipid bilayers and mitochondrial membranes
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    it did cause saturable alterations in lipid packing.
    1 context sentence
    Summary · context
    In this study, using biophysical and computational approaches, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitochondrial membranes.
  4. 04LabIn vitro (cell-free)Activity measurement

    SS‑31 modulated the surface electrostatics of both model and mitochondrial membranes.

    In plain wordsIn lab tests, SS‑31 changed the electric charge at the surface of model and mitochondrial membranes.

    Peptide
    Elamipretide (SS-31)
    Outcome
    MixedMembrane surface electrostatics
    Study

    n: not reported in source

    model lipid bilayers and mitochondrial membranes
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Most notably, SS-31 modulated the surface electrostatics of both model and mitochondrial membranes.
    1 context sentence
    Summary · context
    In this study, using biophysical and computational approaches, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitochondrial membranes.
  5. 05LabIn vitro (cell-free)Activity measurement

    SS‑31 altered divalent cation (calcium) distribution within the membrane interfacial region.

    In plain wordsIn lab tests, SS‑31 changed where calcium sits near the membrane surface.

    Peptide
    Elamipretide (SS-31)
    Outcome
    MixedCalcium distribution in the interfacial region
    Study

    n: not reported in source

    model lipid bilayers and mitochondrial membranes
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    we show that SS-31 alters divalent cation (calcium) distribution within the interfacial region and reduces the energetic burden of calcium stress in mitochondria.
    1 context sentence
    Summary · context
    In this study, using biophysical and computational approaches, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitochondrial membranes.
  6. 06LabIn vitro (cell-free)Activity measurement

    SS‑31 reduced the energetic burden of calcium stress in mitochondria.

    In plain wordsIn lab tests, SS‑31 reduced the energy cost to mitochondria of calcium stress.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseEnergetic burden of calcium stress in mitochondria
    Study

    n: not reported in source

    model lipid bilayers and mitochondrial membranes
    Outcome group
    Mitochondrial function · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    reduces the energetic burden of calcium stress in mitochondria.
    1 context sentence
    Summary · context
    In this study, using biophysical and computational approaches, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitochondrial membranes.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 08:19 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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