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Record W4414935717 · doi:10.1080/27694127.2025.2562429

Influence of skeletal muscle heterogeneity on autophagic signaling and response

2025· review· en· W4414935717 on OpenAlexafffund
Fasih A. Rahman, Joe Quadrilatero

Bibliographic record

VenueAutophagy Reports · 2025
Typereview
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsUniversity of Waterloo
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsSkeletal muscleAutophagyProteostasisOrganelleMyocyteGlycolysisFlux (metallurgy)Lysosome

Abstract

fetched live from OpenAlex

Skeletal muscle is a heterogeneous tissue composed of fibers with distinct contractile, metabolic, and molecular characteristics. This intrinsic heterogeneity influences how individual fibers respond to physiological stimuli, pathological stress, and cellular remodeling processes such as autophagy. Skeletal muscle autophagy is essential for maintaining proteostasis and organelle quality, particularly in high-demand tissues like skeletal muscle. However, emerging evidence indicates that autophagy is not uniformly regulated across all muscles and fibers within a skeletal muscle. Fast/glycolytic fibers, characterized by faster contractile speed and high glycolytic capacity, exhibit greater autophagic flux potentially driven by activation of energy signals, calcium, and redox-sensitive pathways. In contrast, slow/oxidative fibers, characterized by slow contractile speed and higher oxidative metabolism, show lower inducible autophagy despite elevated basal expression of autophagy-related proteins. These differences are compounded by fiber type - specific organelle architecture, recruitment patterns during activity and disuse, and substrate availability and utilization. Further, pathological conditions such as disuse, chronic disease, and myopathies often induce fiber type alterations as well as changes to organelle content and function that are closely associated with changes in autophagy signaling. Additionally, species and strain variability add another layer of complexity, complicating both the interpretation and translational relevance of autophagy studies in skeletal muscle. This review synthesizes current evidence linking skeletal muscle phenotype to autophagy regulation and highlights the need to consider skeletal muscle heterogeneity as a central variable in skeletal muscle autophagy research. A deeper understanding of skeletal muscle type/fiber-specific autophagy will improve our ability to interpret experimental findings and develop targeted interventions for skeletal muscle dysfunction.

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 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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.934
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.023
GPT teacher head0.348
Teacher spread0.325 · 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 teacher head, not a consensus.

Study designOther design
Domainnot available
GenreReview

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

Citations2
Published2025
Admission routes2
Has abstractyes

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