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Record W2803005522 · doi:10.1016/j.celrep.2018.03.098

MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress

2018· article· en· W2803005522 on OpenAlexaff
Neeharika Nemani, Edmund Carvalho, Dhanendra Tomar, Zhiwei Dong, Andrea Ketschek, Sarah L. Breves, Fabián Jaña, Alison M. Worth, Julie Heffler, Palaniappan Palaniappan, Aparna Tripathi, Massimo F. Riitano, Ajay Seelam, Manfred Thomas, Kie Itoh, Shuxia Meng, Hiromi Sesaki, William J. Craigen, Sudarsan Rajan, Santhanam Shanmughapriya, Jeffrey L. Caplan, Benjamin L. Prosser, Donald L. Gill, Peter B. Stathopulos, Gianluca Gallo, David C. Chan, Prashant Mishra, Muniswamy Madesh

Bibliographic record

VenueCell Reports · 2018
Typearticle
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsWestern University
FundersNational Heart, Lung, and Blood InstituteFondo Nacional de Desarrollo Científico, Tecnológico y de Innovación TecnológicaAmerican Historical AssociationNational Science Foundation of Sri LankaChina Scholarship CouncilNational Center for Research ResourcesNational Institute of General Medical SciencesAmerican Heart AssociationNational Institutes of HealthNational Science Foundation
KeywordsMitophagyMitochondrionCell biologyCytosolAutophagyMitochondrial permeability transition poreProgrammed cell deathBiologyC2 domainChemistryApoptosisBiochemistry

Abstract

fetched live from OpenAlex

Mitochondria shape cytosolic calcium ([Ca 2+ ] c ) transients and utilize the mitochondrial Ca 2+ ([Ca 2+ ] m ) in exchange for bioenergetics output. Conversely, dysregulated [Ca 2+ ] c causes [Ca 2+ ] m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca 2+ uptake exhibited elevated [Ca 2+ ] c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca 2+ -induced shape change that is distinct from mitochondrial fission and swelling. [Ca 2+ ] c elevation, but not MCU-mediated Ca 2+ uptake, appears to be essential for the process we term mitochondrial shape transition (MiST). MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca 2+ -dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca 2+ sensor that decodes metazoan Ca 2+ signals as MiST.

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 score0.003
Threshold uncertainty score0.009

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 studies0.0010.001
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.012
GPT teacher head0.259
Teacher spread0.248 · 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

Citations113
Published2018
Admission routes1
Has abstractyes

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