Acetate and hypertonic stress stimulate organelle membrane fission using distinct phosphatidylinositol signals
Bibliographic record
Abstract
ABSTRACT Organelle morphology reflects an equilibrium between membrane fusion and fission that determines size, shape and copy number. By studying the yeast vacuole as a model, the conserved molecular mechanisms responsible for organelle fusion have been revealed. However, a detailed understanding of vacuole fission and how these opposing processes respond to the cell cycle, osmoregulation or metabolism to change morphology remain elusive. Thus, herein we describe a new fluorometric assay to measure vacuole fission in vitro. For proof-of-concept, we use this assay to confirm that acetate, a key intermediary metabolite, triggers vacuole fission in vitro and show that it also blocks homotypic vacuole fusion. The basis of this effect is distinct from hypertonic stress, a known trigger of fission and inhibitor of fusion that inactivates the Rab-GTPase Ypt7: Treatment with the phosphatidylinositol-kinase inhibitor wortmannin or the catalytic domain of the Rab-GAP (GTPase Activating Protein) Gyp1 reveal that fission can be triggered by Ypt7 inactivation alone in absence of hypertonic stress, placing it upstream of PI-3,5-P 2 synthesis and osmosis required for membrane scission. Whereas acetate seems to block PI-4-kinase to possibly increase the pool of PI on vacuole membranes needed to synthesize sufficient PI-3,5-P 2 for fission. Thus, we speculate that both PI-4-P and PI-3-P arms of PI-P signaling drive changes in membrane fission and fusion responsible altering vacuole morphology in response to cellular metabolism or osmoregulation. GRAPHICAL ABSTRACT
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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 | 0.001 |
| 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".