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Record W2363363069 · doi:10.1016/j.celrep.2016.04.050

MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics

2016· article· en· W2363363069 on OpenAlexaff
Dhanendra Tomar, Zhiwei Dong, Santhanam Shanmughapriya, D. A. Koch, Toby P. Thomas, Nicholas E. Hoffman, Shrishiv Timbalia, Samuel J. Goldman, Sarah L. Breves, Daniel P. Corbally, Neeharika Nemani, Joseph P. Fairweather, Allison R. Cutri, Xueqian Zhang, Jianliang Song, Fabián Jaña, Jianhe Huang, Carlos A. Barrero, Joseph E. Rabinowitz, Timothy S. Luongo, Sarah M. Schumacher, Michael E. Rockman, Alexander Dietrich, Salim Merali, Jeffrey L. Caplan, Peter B. Stathopulos, Rexford S. Ahima, Joseph Y. Cheung, Steven R. Houser, Vickas Patel, Vishal M. Gohil, John W. Elrod, Sudarsan Rajan, Muniswamy Madesh

Bibliographic record

VenueCell Reports · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMitochondrial Function and Pathology
Canadian institutionsWestern University
FundersNational Center for Research ResourcesNational Institute of General Medical SciencesNational Institute on Drug AbuseNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteExxonMobil Research and Engineering Company
KeywordsCell biologyAutophagyMitochondrionBioenergeticsMitophagyBiologyUniporterMitochondrial matrixRegulatorNRF1ChemistryBiochemistryCytosolApoptosisMitochondrial biogenesisGene

Abstract

fetched live from OpenAlex

Mitochondrial Ca(2+) Uniporter (MCU)-dependent mitochondrial Ca(2+) uptake is the primary mechanism for increasing matrix Ca(2+) in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1) have severely impaired [Ca(2+)]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca(2+)-dependent mitochondrial metabolism.

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)0.0010.000
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 head0.023
GPT teacher head0.245
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

Citations204
Published2016
Admission routes1
Has abstractyes

Explore more

Same venueCell ReportsSame topicMitochondrial Function and PathologyFrench-language works237,207