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Record W4403763048 · doi:10.1101/2024.10.25.620155

Mitochondrial ETF insufficiency drives neoplastic growth by selectively optimizing cancer bioenergetics

2024· preprint· en· W4403763048 on OpenAlexafffund
David Papadopoli, Ranveer Palia, Predrag Jovanovic, Sébastien Tabariès, Emma Ciccolini, Valérie Sabourin, Sebastian Igelmann, Shannon McLaughlan, Lesley Zhan, HaEun Kim, Nabila Chekkal, Krzysztof J. Szkop, Thierry Bertomeu, Jibin Zeng, Julia Vassalakis, Farzaneh Afzali, Slim Mzoughi, Ernesto Guccione, Mike Tyers, Daina Avizonis, Ola Larsson, Lynne‐Marie Postovit, Sergej Djuranović, Josie Ursini‐Siegel, Peter M. Siegel, Michaël Pollak, Ivan Topisirović

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicATP Synthase and ATPases Research
Canadian institutionsSickKids FoundationUniversity of TorontoUniversité de MontréalThe Metabolomics Innovation CentreMcGill University Health CentreQueen's UniversityMcGill University and Génome Québec Innovation CentreHospital for Sick ChildrenInstitute for Research in Immunology and CancerMcGill University
FundersVetenskapsrådetTerry Fox Foundation
KeywordsBioenergeticsReduction (mathematics)Expression (computer science)Computer scienceBiologyCell biologyMathematics

Abstract

fetched live from OpenAlex

Abstract Mitochondrial electron transport flavoprotein (ETF) insufficiency causes metabolic diseases known as a multiple acyl-CoA dehydrogenase deficiency (MADD). In contrast to muscle, ETFDH is a non-essential gene in acute lymphoblastic leukemia NALM-6 cells, and its expression is reduced across human cancers. ETF insufficiency caused by decreased ETFDH expression limits flexibility of OXPHOS fuel utilization but paradoxically increases cancer cell bioenergetics and accelerates neoplastic growth by activation of the mTORC1/BCL-6/4E-BP1 axis. Collectively, these findings reveal that while ETF insufficiency is rare and has detrimental effects in non-malignant tissues, it is common in neoplasia, where ETFDH downregulation leads to bioenergetic and signaling reprogramming that accelerate neoplastic growth.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.248
Teacher spread0.239 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes2
Has abstractyes

Explore more

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