Disruption of mitochondrial quality control genes promotes caspase-resistant cell survival following apoptotic stimuli

Lade...
Vorschaubild
Dateien
Kushnareva_2-4evsefo3uxyo9.pdf
Kushnareva_2-4evsefo3uxyo9.pdfGröße: 2.29 MBDownloads: 87
Datum
2022
Autor:innen
Kushnareva, Yulia
Moraes, Vivian
Peters, Bjoern
Newmeyer, Donald D.
Kuwana, Tomomi
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Link zur Lizenz
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Gold
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
The Journal of Biological Chemistry (JBC). Elsevier. 2022, 298(4), 101835. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1016/j.jbc.2022.101835
Zusammenfassung

In cells undergoing cell-intrinsic apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically marks an irreversible step in the cell death process. However, in some cases, a subpopulation of treated cells can exhibit a sublethal response, termed “minority MOMP.” In this phenomenon, the affected cells survive, despite a low level of caspase activation and subsequent limited activation of the endonuclease caspase-activated DNase (DNA fragmentation factor subunit beta). Consequently, these cells can experience DNA damage, increasing the probability of oncogenesis. However, little is known about the minority MOMP response. To discover genes that affect the MOMP response in individual cells, we conducted an imaging-based phenotypic siRNA screen. We identified multiple candidate genes whose downregulation increased the heterogeneity of MOMP within single cells, among which were genes related to mitochondrial dynamics and mitophagy that participate in the mitochondrial quality control (MQC) system. Furthermore, to test the hypothesis that functional MQC is important for reducing the frequency of minority MOMP, we developed an assay to measure the clonogenic survival of caspase-engaged cells. We found that cells deficient in various MQC genes were indeed prone to aberrant post-MOMP survival. Our data highlight the important role of proteins involved in mitochondrial dynamics and mitophagy in preventing apoptotic dysregulation and oncogenesis.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690KUSHNAREVA, Yulia, Vivian MORAES, Julian SUESS, Bjoern PETERS, Donald D. NEWMEYER, Tomomi KUWANA, 2022. Disruption of mitochondrial quality control genes promotes caspase-resistant cell survival following apoptotic stimuli. In: The Journal of Biological Chemistry (JBC). Elsevier. 2022, 298(4), 101835. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1016/j.jbc.2022.101835
BibTex
@article{Kushnareva2022Disru-57703,
  year={2022},
  doi={10.1016/j.jbc.2022.101835},
  title={Disruption of mitochondrial quality control genes promotes caspase-resistant cell survival following apoptotic stimuli},
  number={4},
  volume={298},
  issn={0021-9258},
  journal={The Journal of Biological Chemistry (JBC)},
  author={Kushnareva, Yulia and Moraes, Vivian and Suess, Julian and Peters, Bjoern and Newmeyer, Donald D. and Kuwana, Tomomi},
  note={Article Number: 101835}
}
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/123456789/57703">
    <dc:creator>Suess, Julian</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-05-31T09:46:58Z</dcterms:available>
    <dcterms:issued>2022</dcterms:issued>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57703/1/Kushnareva_2-4evsefo3uxyo9.pdf"/>
    <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by/4.0/"/>
    <dc:creator>Peters, Bjoern</dc:creator>
    <dc:creator>Kuwana, Tomomi</dc:creator>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57703"/>
    <dc:contributor>Peters, Bjoern</dc:contributor>
    <dcterms:title>Disruption of mitochondrial quality control genes promotes caspase-resistant cell survival following apoptotic stimuli</dcterms:title>
    <dc:creator>Newmeyer, Donald D.</dc:creator>
    <dcterms:abstract xml:lang="eng">In cells undergoing cell-intrinsic apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically marks an irreversible step in the cell death process. However, in some cases, a subpopulation of treated cells can exhibit a sublethal response, termed “minority MOMP.” In this phenomenon, the affected cells survive, despite a low level of caspase activation and subsequent limited activation of the endonuclease caspase-activated DNase (DNA fragmentation factor subunit beta). Consequently, these cells can experience DNA damage, increasing the probability of oncogenesis. However, little is known about the minority MOMP response. To discover genes that affect the MOMP response in individual cells, we conducted an imaging-based phenotypic siRNA screen. We identified multiple candidate genes whose downregulation increased the heterogeneity of MOMP within single cells, among which were genes related to mitochondrial dynamics and mitophagy that participate in the mitochondrial quality control (MQC) system. Furthermore, to test the hypothesis that functional MQC is important for reducing the frequency of minority MOMP, we developed an assay to measure the clonogenic survival of caspase-engaged cells. We found that cells deficient in various MQC genes were indeed prone to aberrant post-MOMP survival. Our data highlight the important role of proteins involved in mitochondrial dynamics and mitophagy in preventing apoptotic dysregulation and oncogenesis.</dcterms:abstract>
    <dc:contributor>Moraes, Vivian</dc:contributor>
    <dc:creator>Moraes, Vivian</dc:creator>
    <dc:contributor>Newmeyer, Donald D.</dc:contributor>
    <dc:language>eng</dc:language>
    <dc:contributor>Kuwana, Tomomi</dc:contributor>
    <dc:contributor>Suess, Julian</dc:contributor>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-05-31T09:46:58Z</dc:date>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Kushnareva, Yulia</dc:contributor>
    <dc:rights>Attribution 4.0 International</dc:rights>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/57703/1/Kushnareva_2-4evsefo3uxyo9.pdf"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Kushnareva, Yulia</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Begutachtet
Ja
Diese Publikation teilen