期刊
JOURNAL OF CELL BIOLOGY
卷 218, 期 4, 页码 1319-1334出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201808119
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资金
- Cancer Prevention and Research Institute of Texas Core Facility Support Award [RP170644]
- Cancer Prevention and Research Institute of Texas grant [RP140082]
- Welch Foundation [I-1873]
- Searle Foundation [SSP-2016-1482]
- National Institutes of Health National Institute of General Medical Sciences [GM119768]
- American Federation for Aging Research [A15198]
- University of Texas Southwestern Endowed Scholars Program
Lipid droplets (LDs) serve as cytoplasmic reservoirs for energy-rich fatty acids (FAs) stored in the form of triacylglycerides (TAGs). During nutrient stress, yeast LDs cluster adjacent to the vacuole/lysosome, but how this LD accumulation is coordinated remains poorly understood. The ER protein Mdm1 is a molecular tether that plays a role in clustering LDs during nutrient depletion, but its mechanism of function remains unknown. Here, we show that Mdm1 associates with LDs through its hydrophobic N-terminal region, which is sufficient to demarcate sites for LD budding. Mdm1 binds FAs via its Phoxassociated domain and coenriches with fatty acyl-coenzyme A ligase Faa1 at LD bud sites. Consistent with this, loss of MDM1 perturbs free FA activation and Dgal-dependent synthesis of TAGs, elevating the cellular FA level, which perturbs ER morphology and sensitizes yeast to FA-induced lipotoxicity. We propose that Mdm1 coordinates FA activation adjacent to the vacuole to promote LD production in response to stress, thus maintaining ER homeostasis.
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