Editors' ChoiceCell Biology

Organelle contacts for lipid mobilization

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Science Signaling  24 Sep 2019:
Vol. 12, Issue 600, eaaz5525
DOI: 10.1126/scisignal.aaz5525

Interorganellar cross-talk controls the storage and mobilization of lipids in fruitflies.

Drosophila melanogaster produces and stores lipids in the fat body, an organ that combines the physiological functions of the mammalian liver and adipose tissue. In fat body adipocytes, lipid droplets (LDs) store triacylglycerides (TAGs) that are produced from circulating lipids or by de novo synthesis in the endoplasmic reticulum (ER). Ugrankar et al. found that fat body adipocytes contained both small peripheral LDs (pLDs) associated with the plasma membrane (PM) that decreased in number during fasting, and large cytoplasmic medial LDs (mLDs) that were not affected by fasting. Experiments in which circulating lipids or de novo lipid biogenesis was perturbed were consistent with pLDs storing lipids acquired from the circulation and mLDs storing the products of de novo lipogenesis. Maintenance of the proper size and number of pLDs—but not—mLDs, required cortical actin, the pLD-associated perilipin LSD2, and Snazarus (Snz), a homolog of yeast Mdm1, which is an ER-anchored protein that binds to LDs and couples them to the vacuole. Snz localized to ER-PM contact sites, interacted directly with pLDs, and was required for proper TAG mobilization during fasting in adult flies. Overexpression of Snz increased TAG storage in the fat body, increased the survival of both larvae and adults during fasting, and extended the life span of adults fed a high-sugar diet, consistent with TAG stores acting as a sink for the excess nutrients that contribute to metabolic dysfunction and morbidity. These findings illustrate the importance of organellar contacts in regulating both homeostatic and adaptive cell biological processes.

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