RT Journal Article
SR Electronic
T1 Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 544023
DO 10.1101/544023
A1 Chi-Lun Chang
A1 Aubrey V. Weigel
A1 Maria S. Ioannou
A1 H. Amalia Pasolli
A1 C. Shan Xu
A1 David R. Peale
A1 Gleb Shtengel
A1 Melanie Freeman
A1 Harald F. Hess
A1 Craig Blackstone
A1 Jennifer Lippincott-Schwartz
YR 2019
UL http://biorxiv.org/content/early/2019/02/14/544023.abstract
AB Lipid droplets (LDs) are neutral lipid storage organelles that transfer lipids to various organelles including peroxisomes. Here, we show that the hereditary spastic paraplegia protein M1 Spastin, a membrane-bound AAA ATPase found on LDs, coordinates fatty acid (FA) trafficking from LDs to peroxisomes through two inter-related mechanisms. First, M1 Spastin forms a tethering complex with peroxisomal ABCD1 to promote LD-peroxisome contact formation. Second, M1 Spastin recruits the membrane-shaping ESCRT-III proteins IST1 and CHMP1B to LDs via its MIT domain to facilitate LD-to-peroxisome FA trafficking, possibly through IST1 and CHMP1B modifying LD membrane morphology. Furthermore, M1 Spastin, IST1 and CHMP1B are all required to relieve LDs of lipid peroxidation. M1 Spastin’s dual roles in tethering LDs to peroxisomes and in recruiting ESCRT-components to LD-peroxisome contact sites for FA trafficking may help explain the pathogenesis of diseases associated with defective FA metabolism in LDs and peroxisomes.