MétaCan
Menu
Back to cohort
Record W3111428523 · doi:10.1152/ajpcell.00502.2020

Molecular nature and physiological role of the mitochondrial calcium uniporter channel

2020· review· en· W3111428523 on OpenAlex
B. Rita Alevriadou, Akshar Patel, Megan Noble, Sagnika Ghosh, Vishal M. Gohil, Peter B. Stathopulos, Muniswamy Madesh

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueAmerican Journal of Physiology-Cell Physiology · 2020
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMitochondrial Function and Pathology
Canadian institutionsWestern University
FundersInstitute of Health Services and Policy ResearchNational Center for Research ResourcesNational Institute of General Medical SciencesNational Heart, Lung, and Blood InstituteBarth Syndrome FoundationGovernment of CanadaCanadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of CanadaWelch Foundation
KeywordsMitochondrionCell biologyUniporterMitophagyBiologyAutophagyCardiolipinInner mitochondrial membraneProgrammed cell deathBiochemistryApoptosisPhospholipidCytosol

Abstract

fetched live from OpenAlex

Calcium (Ca 2+ ) signaling is critical for cell function and cell survival. Mitochondria play a major role in regulating the intracellular Ca 2+ concentration ([Ca 2+ ] i ). Mitochondrial Ca 2+ uptake is an important determinant of cell fate and governs respiration, mitophagy/autophagy, and the mitochondrial pathway of apoptosis. Mitochondrial Ca 2+ uptake occurs via the mitochondrial Ca 2+ uniporter (MCU) complex. This review summarizes the present knowledge on the function of MCU complex, regulation of MCU channel, and the role of MCU in Ca 2+ homeostasis and human disease pathogenesis. The channel core consists of four MCU subunits and essential MCU regulators (EMRE). Regulatory proteins that interact with them include mitochondrial Ca 2+ uptake 1/2 (MICU1/2), MCU dominant-negative β-subunit (MCUb), MCU regulator 1 (MCUR1), and solute carrier 25A23 (SLC25A23). In addition to these proteins, cardiolipin, a mitochondrial membrane-specific phospholipid, has been shown to interact with the channel core. The dynamic interplay between the core and regulatory proteins modulates MCU channel activity after sensing local changes in [Ca 2+ ] i , reactive oxygen species, and other environmental factors. Here, we highlight the structural details of the human MCU heteromeric assemblies and their known roles in regulating mitochondrial Ca 2+ homeostasis. MCU dysfunction has been shown to alter mitochondrial Ca 2+ dynamics, in turn eliciting cell apoptosis. Changes in mitochondrial Ca 2+ uptake have been implicated in pathological conditions affecting multiple organs, including the heart, skeletal muscle, and brain. However, our structural and functional knowledge of this vital protein complex remains incomplete, and understanding the precise role for MCU-mediated mitochondrial Ca 2+ signaling in disease requires further research efforts.

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.

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: Bench or experimental · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.959
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0000.000
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.002
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 head0.013
GPT teacher head0.268
Teacher spread0.254 · 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