Spartin-mediated lipid transfer facilitates lipid droplet turnover.

Neng Wan, Zhouping Hong, Matthew A H Parson, Justin L Korfhage, John E Burke, Thomas J Melia, Karin M Reinisch

Proceedings of the National Academy of Sciences of the United States of America 2024 Jan 16

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Lipid droplets (LDs) are organelles critical for energy storage and membrane lipid homeostasis, whose number and size are carefully regulated in response to cellular conditions. The molecular mechanisms underlying lipid droplet biogenesis and degradation, however, are not well understood. The Troyer syndrome protein spartin (SPG20) supports LD delivery to autophagosomes for turnover via lipophagy. Here, we characterize spartin as a lipid transfer protein whose transfer ability is required for LD degradation. Spartin copurifies with phospholipids and neutral lipids from cells and transfers phospholipids in vitro via its senescence domain. A senescence domain truncation that impairs lipid transfer in vitro also impairs LD turnover in cells while not affecting spartin association with either LDs or autophagosomes, supporting that spartin's lipid transfer ability is physiologically relevant. Our data indicate a role for spartin-mediated lipid transfer in LD turnover.

Citation

Neng Wan, Zhouping Hong, Matthew A H Parson, Justin L Korfhage, John E Burke, Thomas J Melia, Karin M Reinisch. Spartin-mediated lipid transfer facilitates lipid droplet turnover. Proceedings of the National Academy of Sciences of the United States of America. 2024 Jan 16;121(3):e2314093121