Identification of seipin-linked factors that act as determinants of a lipid droplet subpopulation
Eisenberg-Bord, Michal, Mari, Muriel, Weill, Uri, Rosenfeld-Gur, Eden, Moldavski, Ofer, Castro, Inês Gomes, Soni, Krishnakant G, Harpaz, Nofar, Levine, Tim P, Futerman, Anthony H, Reggiori, Fulvio, Bankaitis, Vytas A, Schuldiner, Maya and Bohnert, Maria (2018) Identification of seipin-linked factors that act as determinants of a lipid droplet subpopulation. Journal of Cell Biology, 217 (1). pp. 269-282.
Abstract
Functional heterogeneity within the lipid droplet (LD) pool of a single cell has been observed, yet the underlying mechanisms remain enigmatic. Here, we report on identification of a specialized LD subpopulation characterized by a unique proteome and a defined geographical location at the nucleus–vacuole junction contact site. In search for factors determining identity of these LDs, we screened ∼6,000 yeast mutants for loss of targeting of the subpopulation marker Pdr16 and identified Ldo45 (LD organization protein of 45 kD) as a crucial targeting determinant. Ldo45 is the product of a splicing event connecting two adjacent genes (YMR147W and YMR148W/OSW5/LDO16). We show that Ldo proteins cooperate with the LD biogenesis component seipin and establish LD identity by defining positioning and surface-protein composition. Our studies suggest a mechanism to establish functional differentiation of organelles, opening the door to better understanding of metabolic decisions in cells.
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