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Record W2973163219 · doi:10.1126/sciadv.aax8352

Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity

2019· article· en· W2973163219 on OpenAlexaff
Timothy D. Heden, Jordan M. Johnson, Patrick J. Ferrara, Hiroaki Eshima, Anthony R.P. Verkerke, Edward J. Wentzler, Piyarat Siripoksup, Tara M. Narowski, Chanel B. Coleman, Chien‐Te Lin, Terence E. Ryan, Paul T. Reidy, Lisandra E. de Castro Brás, Courtney M. Karner, Charles Burant, J. Alan Maschek, James E. Cox, Douglas G. Mashek, Gabrielle Kardon, Sihem Boudina, Tonya N. Zeczycki, Jared Rutter, Saame Raza Shaikh, Jean E. Vance, Micah J. Drummond, P. Darrell Neufer, Katsuhiko Funai

Bibliographic record

VenueScience Advances · 2019
Typearticle
Languageen
FieldMedicine
TopicAdipose Tissue and Metabolism
Canadian institutionsUniversity of Alberta
FundersNational Center for Complementary and Integrative HealthNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Diabetes and Digestive and Kidney DiseasesNIH Office of the DirectorNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Institutes of HealthWashington University in St. LouisNational Institute of General Medical SciencesAmerican Heart Association
KeywordsSkeletal muscleMitochondrionEnzymeRespiratory systemChemistryCell biologyBiochemistryBiologyMedicineEndocrinologyAnatomy

Abstract

fetched live from OpenAlex

Exercise capacity is a strong predictor of all-cause mortality. Skeletal muscle mitochondrial respiratory capacity, its biggest contributor, adapts robustly to changes in energy demands induced by contractile activity. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are regulated. Here, we show that exercise training or muscle disuse alters mitochondrial membrane phospholipids including phosphatidylethanolamine (PE). Addition of PE promoted, whereas removal of PE diminished, mitochondrial respiratory capacity. Unexpectedly, skeletal muscle-specific inhibition of mitochondria-autonomous synthesis of PE caused respiratory failure because of metabolic insults in the diaphragm muscle. While mitochondrial PE deficiency coincided with increased oxidative stress, neutralization of the latter did not rescue lethality. These findings highlight the previously underappreciated role of mitochondrial membrane phospholipids in dynamically controlling skeletal muscle energetics and function.

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 categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.730
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
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.001

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 head0.019
GPT teacher head0.295
Teacher spread0.276 · 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

Citations101
Published2019
Admission routes1
Has abstractyes

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