The Troyer syndrome protein spartin mediates selective autophagy of lipid droplets.

Abstract

Lipid droplets (LDs) are crucial organelles for energy storage and lipid homeostasis. Autophagy of LDs is an important pathway for their catabolism, but the molecular mechanisms mediating LD degradation by selective autophagy (lipophagy) are unknown. Here we identify spartin as a receptor localizing to LDs and interacting with core autophagy machinery, and we show that spartin is required to deliver LDs to lysosomes for triglyceride mobilization. Mutations in SPART (encoding spartin) lead to Troyer syndrome, a form of complex hereditary spastic paraplegia1. Interfering with spartin function in cultured human neurons or murine brain neurons leads to LD and triglyceride accumulation. Our identification of spartin as a lipophagy receptor, thus, suggests that impaired LD turnover contributes to Troyer syndrome development.

• Authors: Jeeyun Chung, Joongkyu Park, Zon Weng Lai, Talley J Lambert, Ruth C Richards, Jiuchun Zhang, Tobias C Walther, Robert V Farese Jr
• Journal: Nature cell biology (Nat Cell Biol) Vol. 25 Issue 8 Pg. 1101-1110 (08 2023) ISSN: 1476-4679 [Electronic] England
• PMID: 37443287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: © 2023. The Author(s).

Chemical References

• Cell Cycle Proteins
• Carrier Proteins
• Triglycerides

Topics

• Mice
• Humans
• Animals
• Spastic Paraplegia, Hereditary (genetics, metabolism)
• Lipid Droplets (metabolism)
• Cell Cycle Proteins (metabolism)
• Carrier Proteins (metabolism)
• Autophagy
• Triglycerides (metabolism)
• Lipid Metabolism (physiology)