ArticleAutophagy2014
The yeast autophagy protease Atg4 is regulated by thioredoxin.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 112 citations in OpenAlex.
- The ATG4 isotype is a key regulator in CSE/HGenes & diseases · 2027Article
- Intermolecular disulfide bond formation promotes Hsp42 higher-order assembly and shapes client selection in yeast.bioRxiv : the preprint server for biology · 2026Article
- Hydrogen peroxide as a multifaceted regulator of the Atg4 protease and autophagy in the pathogenic fungusFrontiers in fungal biology · 2026Article
- Involvement of the thioredoxin system in multiple diseases: A focus on mechanisms of action in autophagy and ferroptosis (Review).Molecular medicine reports · 2026Review
- PRDX1 promotes testosterone synthesis and attenuates aging via redox regulation of ATG4B to modulate lipophagy.Nature communications · 2025Article
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Cancer-associated mutations in autophagy-related proteins analyzed in yeast and human cells.Autophagy · 2025Article
- ATG8 delipidation is not universally critical for autophagy in plants.Nature communications · 2025Article
- Evolutionary conservation and metabolic significance of autophagy in algae.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- Insights into the Multifaceted Roles of Thioredoxin-1 System: Exploring Knockout Murine Models.Biology · 2024Review
- Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy.International journal of molecular sciences · 2023Article
- Mechanisms controlling plant proteases and their substrates.Cell death and differentiation · 2023Review
- Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy.Life (Basel, Switzerland) · 2022Review
- Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators.Cells · 2022Review
- Article
- How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems.Antioxidants (Basel, Switzerland) · 2022Review
- Monitoring of ATG4 Protease Activity During Autophagy in the Model Microalga Chlamydomonas reinhardtii.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Chlamydomonas proteases: classification, phylogeny, and molecular mechanisms.Journal of experimental botany · 2021Article
- Autophagy Is Involved in the Viability of Overexpressing ThioredoxinAntioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a membrane-trafficking process whereby double-membrane vesicles called autophagosomes engulf and deliver intracellular material to the vacuole for degradation. Atg4 is a cysteine protease with an essential function in autophagosome formation. Mounting evidence suggests that reactive oxygen species may play a role in the control of autophagy and could regulate Atg4 activity but the precise mechanisms remain unclear. In this study, we showed that reactive oxygen species activate autophagy in the model yeast Saccharomyces cerevisiae and unraveled the molecular mechanism by which redox balance controls Atg4 activity. A combination of biochemical assays, redox titrations, and site-directed mutagenesis revealed that Atg4 is regulated by oxidoreduction of a single disulfide bond between Cys338 and Cys394. This disulfide has a low redox potential and is very efficiently reduced by thioredoxin, suggesting that this oxidoreductase plays an important role in Atg4 regulation. Accordingly, we found that autophagy activation by rapamycin was more pronounced in a thioredoxin mutant compared with wild-type cells. Moreover, in vivo studies indicated that Cys338 and Cys394 are required for the proper regulation of autophagosome biogenesis, since mutation of these cysteines resulted in increased recruitment of Atg8 to the phagophore assembly site. Thus, we propose that the fine-tuning of Atg4 activity depending on the intracellular redox state may regulate autophagosome formation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.