Evidence map›Paper›PMID 30909720›Full record

ReviewASN neuro

Mitochondrial Substrate-Level Phosphorylation as Energy Source for Glioblastoma: Review and Hypothesis.

Christos Chinopoulos, Thomas N Seyfried

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in ASN neuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 126 citations in OpenAlex.

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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Christos Chinopoulos1 Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.ORCID 0000-0003-0183-4149
Thomas N Seyfried2 Biology Department, Boston College, Chestnut Hill, MA, USA.
Boston College · USSemmelweis University · HU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AnimalsBrain NeoplasmsEnergy MetabolismGlioblastomaHumansMitochondriaPhosphorylationbioenergeticsgliomastherapiesWarburg

Identifiers

PMID30909720
PMCPMC6311572
OpenAlexW2907510643

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.