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Record W4402709976 · doi:10.1101/2024.09.19.613961

TBC1D24 regulates mitochondria and endoplasmic reticulum-mitochondria contact sites

2024· preprint· en· W4402709976 on OpenAlexafffund
Sara Benhammouda, Justine Rousseau, Philippe M. Campeau, Marc Germain

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsUniversité de MontréalUniversité du Québec à Trois-RivièresUniversité du QuébecCentre Hospitalier Universitaire Sainte-JustineUniversité du Québec à Montréal
FundersFonds de Recherche du Québec - SantéNatural Sciences and Engineering Research Council of CanadaCourtois Foundation
KeywordsEndoplasmic reticulumMitochondrionCell biologyChemistryBiology

Abstract

fetched live from OpenAlex

Abstract The RabGAP protein TBC1D24 is mutated in several neurological disorders including DOORS syndrome (Deafness, Onycho-Osteodystrophy, Mental Retardation, Seizures). Although TBC1D24 comprises two highly conserved domains — the Tre2/Bub2/Cdc16 (TBC) domain and the TLDc domain — both of which seem to play critical roles in cellular functions, its exact physiological function within the cell remains poorly understood. Here, we show that TBC1D24 affects mitochondrial structure and activity. Specifically, both primary fibroblasts from patients with TBC1D24 mutations and cells in which TBC1D24 has been knocked down exhibit fragmented mitochondria, decreased ATP production, and reduced mitochondrial membrane potential. Importantly, loss or mutation of TBC1D24 also alters sites of contact between the endoplasmic reticulum (ER) and mitochondria (ERMCS). These sites are vital for mitochondrial fusion and fission processes, which regulate mitochondrial dynamics and, consequently, mitochondrial activity. Altogether, our results uncover a new role for TBC1D24 in the regulation of mitochondrial functions and ERMCS which likely contribute to the neurological dysfunction present in affected patients.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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 head0.010
GPT teacher head0.233
Teacher spread0.223 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations1
Published2024
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicAutophagy in Disease and Therapy→French-language works237,207→