Details

Autor(en) / Beteiligte

• Hussain, Syed S.
• Tran, Tuyet-Minh
• Ware, Timothy B.
• Luse, Melissa A.
• Prevost, Christopher T.
• Ferguson, Ashley N.
• Kashatus, Jennifer A.
• Hsu, Ku-Lung
• Kashatus, David F.

Titel

RalA and PLD1 promote lipid droplet growth in response to nutrient withdrawal

Ist Teil von

• Cell reports (Cambridge), 2021-07, Vol.36 (4), p.109451-109451, Article 109451

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •RalA and PLD1 are necessary for starvation-induced lipid droplet (LD) formation•RalA recruits PLD1 to lysosomes to promote LD accumulation during starvation•Inhibition of RalA or PLD1 prevents PLIN3 redistribution to growing LDs•PLD1 activity and PA are required for LD accumulation and PLIN3 localization on LDs Lipid droplets (LDs) are dynamic metabolic hubs that undergo changes in size, number, and abundance in response to cellular nutritional cues. Hussain et al. identify the small GTPase RalA and its interacting partner PLD1 as important regulators of LD accumulation in response to nutrient starvation.