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DC Field | Value | Language |
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dc.contributor.author | Farrugia, Maria Ylenia | - |
dc.contributor.author | Ghio, Stephanie | - |
dc.contributor.author | Camilleri, Angelique | - |
dc.contributor.author | Farrugia, Claude | - |
dc.contributor.author | Cauchi, Ruben J. | - |
dc.contributor.author | Cappelli, Sara | - |
dc.contributor.author | Chiti, Fabrizio | - |
dc.contributor.author | Vassallo, Neville | - |
dc.contributor.author | Caruana Grech Perry, Mario | - |
dc.date.accessioned | 2022-02-04T18:25:22Z | - |
dc.date.available | 2022-02-04T18:25:22Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Farrugia, M. Y., Caruana, M., Ghio, S., Camilleri, A., Farrugia, C., Cauchi, R. J., Cappelli, S., Chiti, F., & Vassallo, N. (2020). Toxic oligomers of the amyloidogenic HypF-N protein form pores in mitochondrial membranes. Scientific Reports, 10(1), 17733 | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/88349 | - |
dc.description.abstract | Studies on the amyloidogenic N-terminal domain of the E. coli HypF protein (HypF-N) have contributed significantly to a detailed understanding of the pathogenic mechanisms in neurodegenerative diseases characterised by the formation of misfolded oligomers, by proteins such as amyloid-β, α-synuclein and tau. Given that both cell membranes and mitochondria are increasingly recognised as key targets of oligomer toxicity, we investigated the damaging effects of aggregates of HypF-N on mitochondrial membranes. Essentially, we found that HypF-N oligomers characterised by high surface hydrophobicity (type A) were able to trigger a robust permeabilisation of mito-mimetic liposomes possessing cardiolipin-rich membranes and dysfunction of isolated mitochondria, as demonstrated by a combination of mitochondrial shrinking, lowering of mitochondrial membrane potential and cytochrome c release. Furthermore, using single-channel electrophysiology recordings we obtained evidence that the type A aggregates induced currents reflecting formation of ion-conducting pores in mito-mimetic planar phospholipid bilayers, with multi-level conductances ranging in the hundreds of pS at negative membrane voltages. Conversely, HypF-N oligomers with low surface hydrophobicity (type B) could not permeabilise or porate mitochondrial membranes. These results suggest an inherent toxicity of membrane-active aggregates of amyloid-forming proteins to mitochondria, and that targeting of oligomer-mitochondrial membrane interactions might therefore afford protection against such damage. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.rights | info:eu-repo/semantics/openAccess | en_GB |
dc.subject | Amyloid -- Metabolism | en_GB |
dc.subject | Amyloid beta-protein precursor -- Metabolism | en_GB |
dc.subject | Carboxylic acids -- Analysis | en_GB |
dc.subject | Escherichia coli -- Metabolism | en_GB |
dc.subject | Hydrophobic surfaces | en_GB |
dc.subject | Hydrophilidae | en_GB |
dc.subject | Bilayer lipid membranes | en_GB |
dc.subject | Mitochondria | en_GB |
dc.subject | Mitochondrial membranes | en_GB |
dc.subject | Nervous system -- Diseases | en_GB |
dc.subject | Proteins -- Conformation | en_GB |
dc.subject | Structure-activity relationships (Biochemistry) | en_GB |
dc.subject | Alpha-synuclein | en_GB |
dc.title | Toxic oligomers of the amyloidogenic HypF-N protein form pores in mitochondrial membranes | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1038/s41598-020-74841-z | - |
dc.publication.title | Scientific Reports | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
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Toxic_oligomers_of_the_amyloidogenic_HypF_N_protein_form_pores_in_mitochondrial_membranes.pdf | 1.28 MB | Adobe PDF | View/Open |
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