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Record W3197125680 · doi:10.1073/pnas.2025932118

Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy

2021· article· en· W3197125680 on OpenAlexafffund
Joshua C. Drake, Rebecca J. Wilson, Rhianna C. Laker, Yuntian Guan, Hannah R. Spaulding, Anna S. Nichenko, Huayu Shang, Maya V. Dorn, Kian A Huang, Mei Zhang, Aloka B. Bandara, Matthew H. Brisendine, Jennifer A. Kashatus, Poonam Sharma, A. P. Young, Jitendra Gautam, Ruofan Cao, Horst Wallrabe, Paul Chang, Michael Wong, Eric M. Desjardins, Simon A. Hawley, George J. Christ, David F. Kashatus, Clint L. Miller, Matthew J. Wolf, Ammasi Periasamy, Gregory R. Steinberg, D. Grahame Hardie, Zhen Yan

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2021
Typearticle
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsMcMaster University
FundersNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Heart, Lung, and Blood InstituteNational Institute on AgingCanadian Institutes of Health ResearchUniversity of VirginiaCanadian HIV Trials Network, Canadian Institutes of Health ResearchWellcome TrustNational Institutes of HealthDiabetes CanadaNational Center for Research ResourcesAmerican Heart Association
KeywordsMitophagyAMPKSkeletal muscleCell biologyMitochondrionEndoplasmic reticulumBiologyEndocrinologyAutophagyBiochemistryApoptosisProtein kinase A

Abstract

fetched live from OpenAlex

Mitochondria form a complex, interconnected reticulum that is maintained through coordination among biogenesis, dynamic fission, and fusion and mitophagy, which are initiated in response to various cues to maintain energetic homeostasis. These cellular events, which make up mitochondrial quality control, act with remarkable spatial precision, but what governs such spatial specificity is poorly understood. Herein, we demonstrate that specific isoforms of the cellular bioenergetic sensor, 5' AMP-activated protein kinase (AMPKα1/α2/β2/γ1), are localized on the outer mitochondrial membrane, referred to as mitoAMPK, in various tissues in mice and humans. Activation of mitoAMPK varies across the reticulum in response to energetic stress, and inhibition of mitoAMPK activity attenuates exercise-induced mitophagy in skeletal muscle in vivo. Discovery of a mitochondrial pool of AMPK and its local importance for mitochondrial quality control underscores the complexity of sensing cellular energetics in vivo that has implications for targeting mitochondrial energetics for disease treatment.

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 score0.001
Threshold uncertainty score0.003

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.025
GPT teacher head0.315
Teacher spread0.290 · 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

Citations196
Published2021
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicAutophagy in Disease and TherapyFrench-language works237,207