Crosstalk between the Ino80 complex and TOR signaling drives fungal adaptation to hypoxia through chromatin remodeling
Bibliographic record
Abstract
Abstract In the human host, the opportunistic yeast Candida albicans must adapts to niches that vary markedly in oxygen tension, ranging from the hypoxic gastrointestinal and vaginal tracts to more oxygen-rich niches such as the skin. Thriving across this spectrum requires the capacity to dynamically rewire core metabolic pathways in response to fluctuating oxygen levels. Yet, despite the central role of oxygen in shaping fungal metabolism and fitness, the genetic basis underlying hypoxic adaptation in C. albicans remains incompletely understood. Here, we performed a genetic screen to identify genes required for adaptation to hypoxia (5% O 2 ). This comprehensive approach revealed numerous genes spanning diverse metabolic and stress-related functions that are essential for optimal growth under oxygen-limiting conditions. Notably, this study uncovers a previously unrecognized role for the TOR (Target of Rapamycin) signaling pathway and the chromatin-remodeling complex Ino80 in orchestrating the fungal adaptive response to hypoxia. Integration of ino80 mutant transcriptomic data with Ino80 DNA-binding and nucleosome-occupancy profiles under conditional INO80 depletion revealed that this chromatin remodeler regulates the cellular phosphate demand associated with hypoxic exposure. The similarity between chromatin accessibility changes following TOR1 and INO80 depletion further suggests that Ino80 acts in concert with the TOR pathway to support growth and maintain phosphate homeostasis under low-oxygen conditions. Collectively, these findings provide new insight into how nutrient and oxygen signaling converge on chromatin remodeling, offering a mechanistic framework for understanding the regulatory logic underlying hypoxic adaptation in pathogenic fungi. Importance Candida albicans is an opportunistic fungal pathogen that colonizes diverse host niches, many of which are oxygen-limited. Understanding how this organism adapts to hypoxia is critical for elucidating the mechanisms underpinning both commensalism and pathogenicity of this yeast. Here, we reveal that the TOR signaling pathway and the Ino80 chromatin-remodeling complex are key regulators of fungal growth under low-oxygen conditions. Our data show that Ino80 coordinates phosphate homeostasis during hypoxia and functions in concert with TOR to maintain chromatin accessibility and metabolic adaptation. Our results uncover how oxygen and nutrient cues converge on chromatin remodeling, providing a framework for understanding how C. albicans and other human-associated fungi modulate their physiology to thrive and evolve in diverse host environments.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".