LDO proteins and Vac8 form a vacuole-lipid droplet contact site to enable starvation-induced lipophagy in yeast
Lipid droplets (LDs) are fat storage organelles critical for energy and lipid metabolism. Upon nutrient exhaustion, cells consume LDs via gradual lipolysis or via lipophagy, the en bloc uptake of LDs into the vacuole. Here, we show that LDs dock to the vacuolar membrane via a contact site that is re...
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Veröffentlicht in: | Developmental cell 2024-03, Vol.59 (6), p.759-775.e5 |
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Zusammenfassung: | Lipid droplets (LDs) are fat storage organelles critical for energy and lipid metabolism. Upon nutrient exhaustion, cells consume LDs via gradual lipolysis or via lipophagy, the en bloc uptake of LDs into the vacuole. Here, we show that LDs dock to the vacuolar membrane via a contact site that is required for lipophagy in yeast. The LD-localized LDO proteins carry an intrinsically disordered region that directly binds vacuolar Vac8 to form vCLIP, the vacuolar-LD contact site. Nutrient limitation drives vCLIP formation, and its inactivation blocks lipophagy, resulting in impaired caloric restriction-induced longevity. We establish a functional link between lipophagy and microautophagy of the nucleus, both requiring Vac8 to form respective contact sites upon metabolic stress. In sum, we identify the tethering machinery of vCLIP and find that Vac8 provides a platform for multiple and competing contact sites associated with autophagy.
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•LDO proteins bind Vac8 to form vCLIP, the vacuole-lipid droplet contact site•Nutrient exhaustion drives vCLIP formation to promote lipophagy•vCLIP is critical for lipophagy and supports caloric-restriction-induced longevity•Disruption of vCLIP induces NVJ expansion and microautophagy of the nucleus
Álvarez-Guerra et al. identify the tethering machinery of the membrane contact site that enables lipid droplet consumption via lipophagy. They show that nutrient exhaustion drives the formation of vCLIP, the vacuole-lipid droplet contact site established by the LDO proteins that bind vacuolar Vac8. |
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ISSN: | 1534-5807 1878-1551 1878-1551 |
DOI: | 10.1016/j.devcel.2024.01.014 |