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Record W4306698261 · doi:10.7554/elife.78915

Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors

2022· article· en· W4306698261 on OpenAlexafffund
Alba Timón‐Gómez, Alexandra L. Scharr, Nicholas Y Wong, Erwin Ni, Arijit Roy, Min Liu, Julisia Chau, Jack L Lampert, Homza Hireed, Noah S. Kim, Masood Jan, Alexander R. Gupta, Ryan W. Day, James M. Gardner, Richard J. A. Wilson, Antoni Barrientos, Andy J. Chang

Bibliographic record

VenueeLife · 2022
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience of respiration and sleep
Canadian institutionsHotchkiss Brain InstituteAlberta Children's HospitalUniversity of Calgary
FundersNational Institute of General Medical SciencesUniversity of California, San FranciscoNational Institutes of HealthCanadian Institutes of Health ResearchAlberta Innovates - Health SolutionsNational Institute of Allergy and Infectious DiseasesMuscular Dystrophy Association
KeywordsCarotid bodyGlomus cellChemoreceptorMitochondrionHypoxia (environmental)Cell biologyBiologyHypoxic ventilatory responseReactive oxygen speciesPeripheral chemoreceptorsOxygenHomeostasisEndocrinologyInternal medicineNeuroscienceRespiratory systemChemistryReceptorBiochemistryAnatomyMedicineElectrophysiology

Abstract

fetched live from OpenAlex

Mammalian carotid body arterial chemoreceptors function as an early warning system for hypoxia, triggering acute life-saving arousal and cardiorespiratory reflexes. To serve this role, carotid body glomus cells are highly sensitive to decreases in oxygen availability. While the mitochondria and plasma membrane signaling proteins have been implicated in oxygen sensing by glomus cells, the mechanism underlying their mitochondrial sensitivity to hypoxia compared to other cells is unknown. Here, we identify HIGD1C, a novel hypoxia-inducible gene domain factor isoform, as an electron transport chain complex IV-interacting protein that is almost exclusively expressed in the carotid body and is therefore not generally necessary for mitochondrial function. Importantly, HIGD1C is required for carotid body oxygen sensing and enhances complex IV sensitivity to hypoxia. Thus, we propose that HIGD1C promotes exquisite oxygen sensing by the carotid body, illustrating how specialized mitochondria can be used as sentinels of metabolic stress to elicit essential adaptive behaviors.

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 score0.006

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 integrity0.0000.001
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 head0.029
GPT teacher head0.266
Teacher spread0.236 · 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

Citations19
Published2022
Admission routes2
Has abstractyes

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