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LDO proteins and Vac8 form a vacuole-lipid droplet contact site to enable starvation-induced lipophagy in yeast

Álvarez-Guerra, Irene; Block, Emma; Broeskamp, Filomena; Gabrijelčič, Sonja; Infant, Terence; de Ory, Ana; Habernig, Lukas; ... Büttner, Sabrina; + view all (2024) LDO proteins and Vac8 form a vacuole-lipid droplet contact site to enable starvation-induced lipophagy in yeast. Developmental Cell 10.1016/j.devcel.2024.01.014. (In press). Green open access

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Abstract

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.

Type: Article
Title: LDO proteins and Vac8 form a vacuole-lipid droplet contact site to enable starvation-induced lipophagy in yeast
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.devcel.2024.01.014
Publisher version: https://doi.org/10.1016/j.devcel.2024.01.014
Language: English
Additional information: © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Ldo16, Ldo45, NVJ, lipid droplets, lipophagy, membrane contact sites, nucleus-vacuole junction, nutrient limitation, vCLIP, vacuole-lipid droplet contact site
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10187477
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