Uncovering the Role of Eaf1 in the Delicate Balance of Lipid Droplet Synthesis and Membrane Composition in <i>Saccharomyces cerevisiae</i>
Bibliographic record
Abstract
The yeast lysine acetyltransferase, NuA4, is known to be critical important to regulating a variety of cell functions through acetylation of protein targets, resulting in changes in localization, function and/or abundance of its target proteins. Most recently, we have discovered a fascinating role for NuA4 in establishing the balance between lipid droplet formation and phospholipid availability for organelle and cell membranes. This was first discovered upon deletion of the main scaffolding subunit of NuA4 which resulting a strange extension of the nuclear membrane, commonly known as a nuclear flare. This occurs in over 50% of eaf1 cells, compared to only 4% in wild type (WT) cells . Under normal conditions, nuclear flares are primarily detected during mitotic arrest where nuclear membrane production continues unchecked, resulting in excess membrane and nuclear flares. However, nuclear flares in eaf1 cells are detected throughout the cell cycle, suggesting a gross dysregulation of lipid phospholipid production in the absence of NuA4. In addition to nuclear flares, the loss of the NuA4 complex causes significant effects to the vacuole. I have seen experimentally that 60% of all eaf1 cells exhibited severe defects in vacuole fusion, containing more than 10 vacuolar lobes, compared to 7% in WT cells. To further understand this regulation, we set out to find a potential protein target of NuA4‐dependant acetylation that could be the potential link between NuA4 and lipid production. Sitting at the cross‐roads between lipid droplet formation and membrane phospholipid production, phosphatidic acid phosphohydrolase 1 (Pah1) acts as a regulator for lipid biosynthesis in S. cerevisiae . Specifically, Pah1 converts a key metabolite, phosphatidic acid (PA) into diacylglycerol (DAG), which is then subsequently processed to form TAG and stored in lipid droplets. Additionally, it has recently been shown that NuA4 acetylates Pah1, which provides a direct mechanism behind this regulation. We hypothesize that acetylation of Pah1 is required to target the protein to the nuclear and vacuolar membrane. We have seen that upon deletion of EAF1, Pah1 3xGFP has an increase abundance in the cytoplasm and becomes localized to distinct punctate structures in the cell. Suggesting a dramatic change in its localization in the absence of acetylation. Additionally, through use of DAG biosensors, we have seen a drastic movement of DAG pools from the vacuolar membrane to the cytosol and plasma membrane in eaf1 cells. This could explain the defects in vacuole fusion. In its entirety, it has become clear that NuA4 is critical to regulating lipid availability for membranes, and determining the resulting membrane composition. We hope to further characterize the specific relationship between NuA4 and Pah1, in order to determine the how acetylation by NuA4 can affect lipid production for droplets and membranes.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".