Diacylglycerol links lipid droplets and tubular ER during growth resumption from stationary phase
Notice bibliographique
Résumé
Diacylglycerol (DAG) is a key signaling lipid and intermediate in lipid metabolism. Stress and nutritional conditions that induce DAG synthesis also promote triacylglycerol (TAG) production and biogenesis of lipid droplets (LDs) in budding yeast. Compared to our knowledge on the spatiotemporal details leading to DAG channeling into TAG synthesis and LD emergence, we know significantly less on how DAG produced from TAG lipolysis is directed towards synthesis of phospholipids for membrane proliferation. Upon re‐entry of growth from stationary phase TAG lipolysis is mainly supported by LD‐resident lipases, providing fatty acids and DAG precursors for membrane lipid synthesis to boost rapid growth. How the metabolic flux of DAG is channeled into phospholipid synthesis while its conversion back to TAG is prevented is not well understood. It has been suggested that turnover of LDs requires a functional interaction with the ER. We monitored DAG localization in live yeast during growth resumption from stationary phase using a fluorescent DAG sensor (C1δ‐GFP). Remarkably, in the first hours after growth restarted, a diverse array of DAG‐enriched liquid ordered microdomains associated with the vacuolar membrane were observed. The formation of these domains was dependent on LD‐resident lipases Tgl3, Tgl4 and the vacuolar lipase Atg15. DAG puncta appeared adjacent to LDs positioned at vertex rings formed around apposed vacuolar membranes. Few of these DAG rich structures were found tightly associated with purified LDs obtained one hour after growth resumption. During LD purification, we identified a subphase lying beneath the LD floating layer, highly enriched in C1δ‐GFP. To gain insight into the nature of this fraction, we performed a detergent‐free immunoisolation approach to obtain membranes enriched in the DAG sensor using GFP‐Trap technology followed by proteomic analysis. A significant enrichment of proteins localized to the endoplasmic reticulum (ER) was identified. Notably, a set of structural proteins critical for the formation of tubular ER were enriched in this group. Additionally, the KEGG metabolic categories of glycerophospholipid, sphingolipid, and sterol metabolism were significantly enriched. Combined approaches using yeast genetics and pharmacological tools to study the effect of altering lipid homeostasis in all three of these categories to study their impact on DAG distribution were used. Our results suggest that DAG produced from TAG catabolism during growth resumption from stationary phase links LD consumption with the tubular ER, where a hub of lipid metabolic enzymes representing all three eukaryotic classes converge. Support or Funding Information This work was funded by the Natural Sciences and Engineering Research Council of Canada to VZ and by an International Eyes High Doctoral and Dean's Doctoral Award from the University of Calgary to SG and Queen Elizabeth graduate awards to MLSP and BNS. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,001 |
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 ».