ArticleBritish journal of pharmacology2014
Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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Who cites it
192 citing papers in PubMed, 301 citations in OpenAlex.
- Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial.Neurology · 2023Trial
- Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome.Orphanet journal of rare diseases · 2022Trial
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- Elamipretide Rejuvenates Oocyte Quality and Restores Female Fertility During Reproductive Aging.Aging cell · 2026Article
- Intranasal Administration of an Arginine-Enriched Penetratin Peptide Confers Neuroprotection via Mitochondrial Functional Modulation in a Genetic Parkinson's Disease Model.CNS neuroscience & therapeutics · 2026Article
- Cardiolipin as a Signaling Hub: Evolutionary Conservation and Programmable Platforms Coupling Mitochondrial Stress to Cell Fate.International journal of molecular sciences · 2026Review
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence.Biology · 2026Article
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- Mitochondrial translational control in cardiovascular diseases: from mechanisms to therapies.Redox biology · 2026Review
- Sensing of cardiolipin exposure on plasma membranes of apoptotic cells by EryA-mCherry protein.The FEBS journal · 2026Article
- Review
- Bimodal regulation and precision therapy of neutrophil extracellular traps in liver ischemia-reperfusion injury: recent advances.Frontiers in immunology · 2026Review
- Recent Advances in Mitochondria-Targeted Nano-Drug Delivery Systems for Cancer Therapy.International journal of nanomedicine · 2026Review
- Novel therapeutic strategies targeting mitochondrial quality control for metabolic dysfunction-associated steatotic liver disease.Frontiers in physiology · 2026Review
- Targeting ANT1 to regulate PINK1/Parkin-mediated mitophagy is an effective treatment of trauma-induced tendon heterotopic ossification.Journal of orthopaedic translation · 2025Article
- Review
- 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
132 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeCardiolipin plays an important role in mitochondrial respiration and cardiolipin peroxidation is associated with age-related diseases. Hydrophobic interactions between cytochrome c and cardiolipin converts cytochrome c from an electron carrier to a peroxidase. In addition to cardiolipin peroxidation, this impedes electron flux and inhibits mitochondrial ATP synthesis. SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2 ) selectively binds to cardiolipin and inhibits cytochrome c peroxidase activity. Here, we examined whether SS-31 also protected the electron carrier function of cytochrome c. EXPERIMENTAL APPROACH: Interactions of SS-31 with cardiolipin were studied using liposomes and bicelles containing phosphatidylcholine alone or with cardiolipin. Structural interactions were assessed by fluorescence spectroscopy, turbidity and nuclear magnetic resonance. Effects of cardiolipin on electron transfer kinetics of cytochrome c were determined by cytochrome c reduction in vitro and oxygen consumption using mitoplasts, frozen and fresh mitochondria. KEY
resultsSS-31 interacted only with liposomes and bicelles containing cardiolipin in about 1:1 ratio. NMR studies demonstrated that the aromatic residues of SS-31 penetrated deep into cardiolipin-containing bilayers. SS-31 restored cytochrome c reduction and mitochondrial oxygen consumption in the presence of added cardiolipin. In fresh mitochondria, SS-31 increased state 3 respiration and efficiency of ATP synthesis. CONCLUSIONS AND IMPLICATIONS: SS-31 selectively targeted cardiolipin and modulated its interaction with cytochrome c. SS-31 inhibited the cytochrome c/cardiolipin complex peroxidase activity while protecting its ability to serve as an electron carrier, thus optimizing mitochondrial electron transport and ATP synthesis. This novel class of cardiolipin therapeutics has the potential to restore mitochondrial bioenergetics for treatment of numerous age-related diseases.
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