Cdc48 plays a crucial role in redox homeostasis through dynamic reshaping of its interactome during early stationary phase
Bibliographic record
Abstract
Most microbial cells on earth predominantly exist in non-proliferating, dormant conditions, such as the stationary state. The stationary phase is a crucial stage during the cellular lifespan, which requires homeostatic rewiring for long-term viability and rapid responses to environmental changes. Here, we show that entry to the stationary phase in yeast is accompanied by increased cytosolic and mitochondrial oxidation, imposing stress on the proteostasis network. We establish a functional link between redox and protein homeostasis, mediated by a key protein quality control member, Cdc48/p97/VCP. Comparative proteomic analysis of post-mitotic yeast cells reveals that while the global proteome remains largely stable during the first stages of stationary phase, the Cdc48 interactome undergoes significant remodeling, including altered interactions with antioxidants and its cofactors Shp1/Ubx1 and Ubx2. To challenge yeast Cdc48's capacity as a redox-switch protein during the early stages of the stationary phase, we utilized redox proteomics to map changes in reversible oxidation modification on Cdc48's cysteines upon entry to the stationary phase. We revealed the temporal and reversible oxidation of Cdc48-Cys115 as a key regulatory event essential for stationary-phase survival and interactome modulation. Cys115-to-serine mutation significantly reduced longevity and increased oxidative stress sensitivity, correlating with disrupted interactions between Cdc48 and antioxidants, and cofactor Shp1, specifically with the phosphorylated form of Shp1. Taken together, these findings identify a new thiol switch protein in the protein degradation pathway, while further defining novel roles for Cdc48 in reshaping the proteome during the yeast stationary phase.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".