Journal
CELL REPORTS
Volume 36, Issue 4, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109451
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- NCI [1R01CA200755]
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Research has shown that the small GTPase RalA facilitates lipid droplet growth during nutrient depletion by recruiting phospholipase D1 to lysosomes. This localized production of phosphatidic acid by PLD1 leads to the recruitment of perilipin 3 to expanding lipid droplets.
Lipid droplets (LDs) are dynamic organelles that undergo dynamic changes in response to changing cellular conditions. During nutrient depletion, LD numbers increase to protect cells against toxic fatty acids generated through autophagy and provide fuel for beta-oxidation. However, the precise mechanisms through which these changes are regulated have remained unclear. Here, we show that the small GTPase RalA acts downstream of autophagy to directly facilitate LD growth during nutrient depletion. Mechanistically, RalA performs this function through phospholipase D1 (PLD1), an enzyme that converts phosphatidylcholine (PC) to phosphatidic acid (PA) and that is recruited to lysosomes during nutrient stress in a RalA-dependent fashion. RalA inhibition prevents recruitment of the LD-associated protein perilipin 3, which is required for LD growth. Our data support a model in which RalA recruits PLD1 to lysosomes during nutrient deprivation to promote the localized production of PA and the recruitment of perilipin 3 to expanding LDs.
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