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Record W3022740829 · doi:10.1096/fj.201903235r

Disruption of mitochondrial dynamics increases stress resistance through activation of multiple stress response pathways

2020· article· en· W3022740829 on OpenAlexafffund
Emily Machiela, Thomas Liontis, Dylan J. Dues, Paige Rudich, Annika Traa, Leslie Wyman, Corah Kaufman, Jason Cooper, Leira Lew, Saravanapriah Nadarajan, Megan M. Senchuk, Jeremy M. Van Raamsdonk

Bibliographic record

VenueThe FASEB Journal · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMitochondrial Function and Pathology
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersNational Institute of General Medical SciencesNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchNational Institutes of Health
KeywordsMitochondrial fissionmitochondrial fusionMitochondrionCell biologyBiologyOrganelleOxidative stressMitochondrial DNAGeneGeneticsBiochemistry

Abstract

fetched live from OpenAlex

Mitochondria are dynamic organelles that can change shape and size depending on the needs of the cell through the processes of mitochondrial fission and fusion. In this work, we investigated the role of mitochondrial dynamics in organismal stress response. By using C. elegans as a genetic model, we could visualize mitochondrial morphology in a live organism with well-established stress assays and well-characterized stress response pathways. We found that disrupting mitochondrial fission (DRP1/drp-1) or fusion (OPA1/eat-3, MFN/fzo-1) genes caused alterations in mitochondrial morphology that impacted both mitochondrial function and physiologic rates. While both mitochondrial fission and mitochondrial fusion mutants showed increased sensitivity to osmotic stress and anoxia, surprisingly we found that the mitochondrial fusion mutants eat-3 and fzo-1 are more resistant to both heat stress and oxidative stress. In exploring the mechanism of increased stress resistance, we found that disruption of mitochondrial fusion genes resulted in the upregulation of multiple stress response pathways. Overall, this work demonstrates that disrupting mitochondrial dynamics can have opposite effects on resistance to different types of stress. Our results suggest that disruption of mitochondrial fusion activates multiple stress response pathways that enhance resistance to specific stresses.

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)0.001
Version: codex-gemma-dda1882f352aValidation 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 score0.031
Threshold uncertainty score0.354

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
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 head0.021
GPT teacher head0.248
Teacher spread0.227 · 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.

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

Citations55
Published2020
Admission routes2
Has abstractyes

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