ArticleThe Journal of biological chemistry2020
The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 116 citations in OpenAlex.
- Trial
- Elamipretide Rejuvenates Oocyte Quality and Restores Female Fertility During Reproductive Aging.Aging cell · 2026Article
- Mitochondria-Targeted Nanotherapies in Aging Neurodegenerative Disorders: Emerging Prospects and Clinical Potential.Advanced healthcare materials · 2026Review
- Mitochondria-Targeting Metal Complexes: Design Principles, Mechanisms of Action, and Translational Perspectives.Biomolecules · 2026Review
- Tuning the Fire: Context-Dependent Mitochondrial ROS Signaling, Mitohormesis, and Redox-Modulating Interventions.Biomolecules · 2026Review
- Mitoregulin supports mitochondrial membrane integrity and protects against cardiac ischaemia-reperfusion injury.Cardiovascular research · 2026Article
- Recent Advances in Mitochondria-Targeted Nano-Drug Delivery Systems for Cancer Therapy.International journal of nanomedicine · 2026Review
- Cardiolipin remodelling in mitochondrial therapeutics: translational evidence chains from elamipretide to emerging strategies.Frontiers in physiology · 2026Review
- Targeting mitochondria for the treatment of neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Tumor-immune metabolic tug-of-war: from immune escape to targeting metabolic rewiring in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Mitochondria-Targeted Peptides and Bilayer Composition Modulate Membrane Electroporation under Elevated Electrochemical Stress.Langmuir : the ACS journal of surfaces and colloids · 2025Article
- Reprogramming the Mitochondrion in Atherosclerosis: Targets for Vascular Protection.Antioxidants (Basel, Switzerland) · 2025Review
- Targeted nanoliposomal nutrient delivery for human health.World journal of gastrointestinal pharmacology and therapeutics · 2025Review
- Mitochondrial membrane chromatography: Discovery of mitochondrial targeting modulators.Journal of pharmaceutical analysis · 2025Review
- Targeting High-Density Aromatic Peptides to Cardiolipin Optimizes the Mitochondrial Membrane Potential and Inhibits Oxidative Stress.FASEB bioAdvances · 2025Article
- Precision Medicine: Therapeutically Targeting Mitochondrial Alterations in Heart Failure.JACC. Basic to translational science · 2025Review
- Mitochondrial-Targeted Protective Potential of Elamipretide for the In Vitro Production of Porcine Embryos.Animals : an open access journal from MDPI · 2025Article
- Acute mitochondrial reactive oxygen species emissions drive mitochondrial dysfunction after traumatic muscle injury in male mice.American journal of physiology. Cell physiology · 2025Article
- Contemporary insights into elamipretide's mitochondrial mechanism of action and therapeutic effects.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.