Coordinated autophagy modulation overcomes glioblastoma chemoresistance through disruption of mitochondrial bioenergetics

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dc.contributor.authorKriel, Jurgenen_ZA
dc.contributor.authorMuller-Nedebock, Kristianen_ZA
dc.contributor.authorMaarman, Geralden_ZA
dc.contributor.authorMbizana, Siyasangaen_ZA
dc.contributor.authorOjuka, Edwarden_ZA
dc.contributor.authorKlumperman, Berten_ZA
dc.contributor.authorLoos, Benen_ZA
dc.date.accessioned2020-03-16T14:15:02Z
dc.date.available2020-03-16T14:15:02Z
dc.date.issued2018-07-09en_ZA
dc.descriptionCITATION: Kriel, J., 2018. Coordinated autophagy modulation overcomes glioblastoma chemoresistance through disruption of mitochondrial bioenergetics. Scientific Reports, 8:10348, doi:10.1038/s41598-018-28590-9.en_ZA
dc.descriptionThe original publication is available at https://www.nature.comen_ZA
dc.description.abstractGlioblastoma Multiforme (GBM) is known to be one of the most malignant and aggressive forms of brain cancer due to its resistance to chemotherapy. Recently, GBM was found to not only utilise both oxidative phosphorylation (OXPHOS) and aerobic glycolysis, but also depend on the bulk protein degradation system known as macroautophagy to uphold proliferation. Although autophagy modulators hold great potential as adjuvants to chemotherapy, the degree of upregulation or inhibition necessary to achieve cell death sensitisation remains unknown. Therefore, this study aimed to determine the degree of autophagy modulation necessary to impair mitochondrial bioenergetics to the extent of promoting cell death onset. It was shown that coordinated upregulation of autophagy followed by its inhibition prior to chemotherapy decreased electron transfer system (ETS) and oxidative phosphorylation (OXPHOS) capacity, impaired mitochondrial fission and fusion dynamics and enhanced apoptotic cell death onset in terms of cleaved caspase 3 and cleaved PARP expression. Therefore, coordinated autophagy modulation may present a favourable avenue for improved chemotherapeutic intervention in the future.en_ZA
dc.description.urihttps://www.nature.com/articles/s41598-018-28590-9en_ZA
dc.description.versionPublisher's versionen_ZA
dc.format.extent13 pages : illustrationsen_ZA
dc.identifier.citationKriel, J., 2018. Coordinated autophagy modulation overcomes glioblastoma chemoresistance through disruption of mitochondrial bioenergetics. Scientific Reports, 8:10348, doi:10.1038/s41598-018-28590-9en_ZA
dc.identifier.issn2045-2322 (online)en_ZA
dc.identifier.otherdoi:10.1038/s41598-018-28590-9
dc.identifier.urihttp://hdl.handle.net/10019.1/107627en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherNature Researchen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectGlioblastoma multiformeen_ZA
dc.subjectBrain -- Cancer -- Chemotherapyen_ZA
dc.subjectPathogenic microorganismsen_ZA
dc.subjectMitochondrial pathologyen_ZA
dc.titleCoordinated autophagy modulation overcomes glioblastoma chemoresistance through disruption of mitochondrial bioenergeticsen_ZA
dc.typeArticleen_ZA
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