An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

Abstract

Eukaryotic cells store neutral lipids such as triacylglycerol (TAG) in lipid droplets (LDs). Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER). We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG). During LD breakdown in early exponential phase, an ER membrane protein (Ice2p) facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.

Mechanism of liponecrosis, a distinct mode of programmed cell death

“…1 To further verify our hypothesis, we examined how various single-gene-deletion mutations (each eliminating an enzyme involved in POA transport to the ER or in POA incorporation into PL and/or NL within the ER; see refs. [7][8][9][10][11][12][13][14][15][16][17][18] and Fig. S3) influence the susceptibility of yeast to POA-induced liponecrotic PCD.…”

“…S3). [7][8][9][10][11][12][13][14][15][16][17][18] It is conceivable therefore that: (1) POA-containing species of PA, PS, PE, PC and PI could amass within the PM bilayer of yeast treated with POA; and (2) such buildup of POA-containing species of PL within the PM could alter the proper PL asymmetry in the PM bilayer and, thus, could induce the alkaline-pH-and lipid-asymmetryresponsive Rim101 signaling pathway.…”

Mature lipid droplets are accessible to ER luminal proteins

“…Neutral lipid accumulation induces relocalization of integral membrane proteins from the ER to lipid droplets, and these proteins move again back into the ER when neutral lipid pools are degraded Kassan et al, 2013;Wilfling et al, 2013;Zehmer et al, 2009). In addition, intermediates of neutral lipid synthesis and degradation are shuffled between the two compartments to allow growth and shrinkage of lipid droplets, depending on the metabolic needs of the cell (Markgraf et al, 2014). Moreover, lipid droplet size is controlled by the exchange of neutral lipids between lipid droplets, a process that is mediated by members of the CIDE family (Xu et al, 2012a).…”

A defect of the vacuolar putative lipase Atg15 accelerates degradation of lipid droplets through lipolysis

“…Dga1 moves from the ER to LDs to synthesize TAG from DAG in the early stationary phase. 38 In both the wild-type and atg15∆ cells, the Dga1-mCherry signal exhibited ring-shaped patterns characteristic of its ER localization, and it was not colocalized with the signal from BODIPY 493/503 representing LD localization, when the cells were cultured in SC medium for 48 h (Fig. S2B).…”