Show simple item record Chinopoulos, Christos Seyfried Thomas N 2020-03-25T12:39:08Z 2020-03-25T12:39:08Z 2018
dc.identifier.citation journalVolume=10;pagination=1759091418818261, pages: 27;journalTitle=ASN NEURO;journalAbbreviatedTitle=ASN NEURO;
dc.identifier.uri doi:10.1177/1759091418818261
dc.description.abstract Glioblastoma multiforme (GBM) is the most common and malignant of the primary adult brain cancers. Ultrastructural and biochemical evidence shows that GBM cells exhibit mitochondrial abnormalities incompatible with energy production through oxidative phosphorylation (OxPhos). Under such conditions, the mitochondrial F0-F1 ATP synthase operates in reverse at the expense of ATP hydrolysis to maintain a moderate membrane potential. Moreover, expression of the dimeric M2 isoform of pyruvate kinase in GBM results in diminished ATP output, precluding a significant ATP production from glycolysis. If ATP synthesis through both glycolysis and OxPhos was impeded, then where would GBM cells obtain high-energy phosphates for growth and invasion? Literature is reviewed suggesting that the succinate-CoA ligase reaction in the tricarboxylic acid cycle can substantiate sufficient ATP through mitochondrial substrate-level phosphorylation (mSLP) to maintain GBM growth when OxPhos is impaired. Production of high-energy phosphates would be supported by glutaminolysis-a hallmark of GBM metabolism-through the sequential conversion of glutamine -> glutamate -> alpha-ketoglutarate -> succinyl CoA -> succinate. Equally important, provision of ATP through mSLP would maintain the adenine nucleotide translocase in forward mode, thus preventing the reverse-operating F0-F1 ATP synthase from depleting cytosolic ATP reserves. Because glucose and glutamine are the primary fuels driving the rapid growth of GBM and most tumors for that matter, simultaneous restriction of these two substrates or inhibition of mSLP should diminish cancer viability, growth, and invasion.
dc.relation.ispartof urn:issn:1759-0914
dc.title Mitochondrial Substrate-Level Phosphorylation as Energy Source for Glioblastoma: Review and Hypothesis
dc.type Journal Article 2019-01-28T14:27:38Z
dc.language.rfc3066 en
dc.rights.holder NULL
dc.identifier.mtmt 30393781
dc.identifier.wos 000454500200001
dc.contributor.department SE/AOK/I/Orvosi Biokémiai Intézet
dc.contributor.institution Semmelweis Egyetem

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