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Mechanisms of ER Neutral Lipid Flux and Lipid Storage

James A. Olzmann1-3

1 Department of Molecular and Cell Biology 2 Department of Nutritional Sciences & Toxicology 3 Chan Zuckerberg Biohub

Lipid droplets (LDs) are endoplasmic reticulum (ER)-derived organelles that function as dynamic lipid storage depots, sequestering toxic lipids and providing a source of lipids that can be rapidly mobilized for membranes, signaling, and energy. Structurally, LDs consist of a neutral lipid core (mostly triacylglycerol and cholesterol esters) encircled by a phospholipid monolayer that is decorated with integral and peripheral proteins. These LD proteins, such as the perilipins (PLINs), play key roles in regulating LD biogenesis and breakdown, trafficking, and inter-organelle interactions. In this presentation I will discuss a series of CRIPSR-Cas9 loss-of-function screens that advance our understanding of the metabolic state-dependent regulation of LD biogenesis and proteome dynamics. These CRISPR screens provide the foundation for CRISPRlipid (http://crisprlipid.org), an extensible, online data commons for lipid-related functional genomics data. Moreover, the data from our screens provide a phenotype-rich resource for the exploration of LD biology and reveal new mechanisms that control neutral lipid flux in the ER and LD protein stability.


Speakers

James A. Olzmann

University of California, Berkeley