NoxO1 promotes endosome formation and reduces intracellular vesicle processing
Bibliographic record
Abstract
NADPH oxidase organizer 1 (NoxO1) is known as a scaffold cytoplasmic subunit of the reactive oxygen species (ROS) forming Nox1 complex. We previously identified an interaction between NoxO1 and Erbin, a cytosolic scaffold protein that associates with Epidermal Growth Factor Receptor (EGFR), but its ROS-independent roles remain poorly understood. Here, we demonstrate that NoxO1 overexpression remodels the endolysosomal system by expanding early endosomes and lysosomes. A calibrated six-compartment ordinary differential equation model of EGFR trafficking predicts a slowed down intracellular trafficking: NoxO1 overexpression increased internalization rates by 14 % while reducing degradative sorting by 48 %, lysosomal transfer by 24 %, and final degradation by 41 %. Using fluorescent cargo (EGF and BSA), we confirmed enhanced internalization and cargo accumulation in lysosomes, supporting the idea of prolonged lysosomal retention in NoxO1 overexpressing cells. Mechanistically, NoxO1 activated transcription factor EB (TFEB), the master regulator of lysosomal biogenesis, in an Erbin-dependent but ROS independent manner. Proximity ligation assays revealed spatial association of NoxO1, Erbin, EGFR, and TFEB, suggesting a multi-protein regulatory complex. Genetic ablation of Erbin abolished NoxO1-induced increases in early endosome (EEA1) and lysosome (LAMP1) markers, confirming Erbin's essential role. In conclusion, via its interaction with Erbin NoxO1 promotes activation of TFEB, contributes to lysosome formation while delaying cargo degradation.
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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".