Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis

Hanaa Hariri, Natalie Speer, Jade Bowerman, Sean Rogers, Gang Fu, Evan Reetz, Sanchari Datta, J. Ryan Feathers, Rupali Ugrankar, Daniela Nicastro, W. Mike Henne

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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 Dga1-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.

Original languageEnglish (US)
Pages (from-to)1319-1334
Number of pages16
JournalJournal of Cell Biology
Volume218
Issue number4
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis'. Together they form a unique fingerprint.

  • Cite this

    Hariri, H., Speer, N., Bowerman, J., Rogers, S., Fu, G., Reetz, E., Datta, S., Feathers, J. R., Ugrankar, R., Nicastro, D., & Henne, W. M. (2019). Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis. Journal of Cell Biology, 218(4), 1319-1334. https://doi.org/10.1083/jcb.201808119