Uncovering the Role of Eaf1 in the Delicate Balance of Lipid Droplet Synthesis and Membrane Composition in <i>Saccharomyces cerevisiae</i>
Notice bibliographique
Résumé
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.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».