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Record W2990870824 · doi:10.1038/s41419-019-2132-x

Bcl-2-associated athanogene 5 (BAG5) regulates Parkin-dependent mitophagy and cell death

2019· article· en· W2990870824 on OpenAlexafffund
Mitchell L. de Snoo, Erik Loewen Friesen, Yu Tong Zhang, Rebecca Earnshaw, Geneviève Dorval, Minesh Kapadia, Darren M. O’Hara, Victoria Agapova, Hien Chau, Ornella Pellerito, Matthew Y. H. Tang, Xinzhu Wang, Gerold Schmitt‐Ulms, Thomas M. Durcan, Edward A. Fon, Lorraine V. Kalia, Suneil K. Kalia

Bibliographic record

VenueCell Death and Disease · 2019
Typearticle
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsOccupational Cancer Research CentreMcGill UniversityUniversity Health NetworkUniversity of TorontoMontreal Neurological Institute and HospitalToronto Western HospitalCanada Research Chairs
FundersCanadian Institutes of Health ResearchCanadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of CanadaNatural Sciences and Engineering Research Council of CanadaGovernment of Canada
KeywordsMitophagyParkinCell biologyProgrammed cell deathApoptosisCancer researchAutophagyBiologyChemistryGeneticsMedicine

Abstract

fetched live from OpenAlex

As pathogenic Parkin mutations result in the defective clearance of damaged mitochondria, Parkin-dependent mitophagy is thought to be protective against the dopaminergic neurodegeneration observed in Parkinson's disease. Recent studies, however, have demonstrated that Parkin can promote cell death in the context of severe mitochondrial damage by degrading the pro-survival Bcl-2 family member, Mcl-1. Therefore, Parkin may act as a 'switch' that can shift the balance between protective or pro-death pathways depending on the degree of mitochondrial damage. Here, we report that the Parkin interacting protein, Bcl-2-associated athanogene 5 (BAG5), impairs mitophagy by suppressing Parkin recruitment to damaged mitochondria and reducing the movement of damaged mitochondria into the lysosomes. BAG5 also enhanced Parkin-mediated Mcl-1 degradation and cell death following severe mitochondrial insult. These results suggest that BAG5 may regulate the bi-modal activity of Parkin, promoting cell death by suppressing Parkin-dependent mitophagy and enhancing Parkin-mediated Mcl-1 degradation.

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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.031
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

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)0.0000.000

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 head0.229
Teacher spread0.220 · 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 designObservational
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

Citations49
Published2019
Admission routes2
Has abstractyes

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