Publikation: TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis
Dateien
Datum
Autor:innen
Herausgeber:innen
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
DOI (zitierfähiger Link)
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Titel in einer weiteren Sprache
Publikationstyp
Publikationsstatus
Erschienen in
Zusammenfassung
Dysregulated mitochondrial fusion and fission has been implicated in the pathogenesis of numerous diseases. We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function. Disruption of this axis results in a fragmented mitochondrial network and an impaired capacity for energy production via oxidative phosphorylation. Owing to the role of OPA1 in modulating cytochrome c release, TAp73−/− cells display an increased sensitivity to apoptotic cell death, e.g., via BH3-mimetics. We additionally show that the TAp73/OPA1 axis has functional relevance in the upper airway, where TAp73 expression is essential for multiciliated cell differentiation and function. Consistently, ciliated epithelial cells of Trp73 −/− (global p73 knock-out) mice display decreased expression of OPA1 and perturbations of the mitochondrial network, which may drive multiciliated cell loss. In support of this, Trp73 and OPA1 gene expression is decreased in chronic obstructive pulmonary disease (COPD) patients, a disease characterised by alterations in mitochondrial dynamics. We therefore highlight a potential mechanism involving the loss of p73 in COPD pathogenesis. Our findings also add to the growing body of evidence for growth-promoting roles of TAp73 isoforms.
Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
Schlagwörter
Konferenz
Rezension
Zitieren
ISO 690
BUCKLEY, Niall A., Andrew CRAXTON, Xiao-Ming SUN, Emanuele PANATTA, Lucia Giraldez PINON, Sina BEIER, Lajos KALMAR, Ivano AMELIO, L. Miguel MARTINS, Marion MACFARLANE, 2024. TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis. In: Cell Death & Disease. Springer. 2024, 15(11), 807. eISSN 2041-4889. Verfügbar unter: doi: 10.1038/s41419-024-07130-6BibTex
@article{Buckley2024-11-08TAp73-71856, title={TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis}, year={2024}, doi={10.1038/s41419-024-07130-6}, number={11}, volume={15}, journal={Cell Death & Disease}, author={Buckley, Niall A. and Craxton, Andrew and Sun, Xiao-Ming and Panatta, Emanuele and Pinon, Lucia Giraldez and Beier, Sina and Kalmar, Lajos and Amelio, Ivano and Martins, L. Miguel and MacFarlane, Marion}, note={Article Number: 807} }
RDF
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/71856"> <dcterms:issued>2024-11-08</dcterms:issued> <dc:creator>Craxton, Andrew</dc:creator> <dcterms:title>TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis</dcterms:title> <dc:contributor>Beier, Sina</dc:contributor> <dc:creator>Sun, Xiao-Ming</dc:creator> <dc:creator>MacFarlane, Marion</dc:creator> <dc:contributor>Craxton, Andrew</dc:contributor> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/> <foaf:homepage rdf:resource="http://localhost:8080/"/> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/71856/1/Buckley_2-mv2ycb37dodw1.pdf"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dc:contributor>Buckley, Niall A.</dc:contributor> <dc:creator>Buckley, Niall A.</dc:creator> <dc:contributor>MacFarlane, Marion</dc:contributor> <dc:contributor>Pinon, Lucia Giraldez</dc:contributor> <dc:contributor>Amelio, Ivano</dc:contributor> <dc:creator>Martins, L. Miguel</dc:creator> <dc:rights>Attribution 4.0 International</dc:rights> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/71856"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2025-01-14T09:59:22Z</dc:date> <dc:contributor>Panatta, Emanuele</dc:contributor> <dc:contributor>Sun, Xiao-Ming</dc:contributor> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/71856/1/Buckley_2-mv2ycb37dodw1.pdf"/> <dc:contributor>Martins, L. Miguel</dc:contributor> <dc:creator>Kalmar, Lajos</dc:creator> <dc:creator>Pinon, Lucia Giraldez</dc:creator> <dc:creator>Beier, Sina</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dc:contributor>Kalmar, Lajos</dc:contributor> <dc:creator>Amelio, Ivano</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2025-01-14T09:59:22Z</dcterms:available> <dc:creator>Panatta, Emanuele</dc:creator> <dc:language>eng</dc:language> <dcterms:abstract>Dysregulated mitochondrial fusion and fission has been implicated in the pathogenesis of numerous diseases. We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function. Disruption of this axis results in a fragmented mitochondrial network and an impaired capacity for energy production via oxidative phosphorylation. Owing to the role of OPA1 in modulating cytochrome c release, TAp73<sup>−/−</sup> cells display an increased sensitivity to apoptotic cell death, e.g., via BH3-mimetics. We additionally show that the TAp73/OPA1 axis has functional relevance in the upper airway, where TAp73 expression is essential for multiciliated cell differentiation and function. Consistently, ciliated epithelial cells of Trp73 <sup>−/−</sup> (global p73 knock-out) mice display decreased expression of OPA1 and perturbations of the mitochondrial network, which may drive multiciliated cell loss. In support of this, Trp73 and OPA1 gene expression is decreased in chronic obstructive pulmonary disease (COPD) patients, a disease characterised by alterations in mitochondrial dynamics. We therefore highlight a potential mechanism involving the loss of p73 in COPD pathogenesis. Our findings also add to the growing body of evidence for growth-promoting roles of TAp73 isoforms.</dcterms:abstract> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> </rdf:Description> </rdf:RDF>