Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III
Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III
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DOI：
10.1083/jcb.201902061
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发表时间：
2019-08-01
影响因子：
7.8
通讯作者：
Lippincott-Schwartz, Jennifer
中科院分区：
文献类型：
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作者：
Chang, Chi-Lun;Weigel, Aubrey, V;Lippincott-Schwartz, Jennifer
脂滴是一种中性的脂类储存细胞器，可以将脂类转移到包括过氧化物体在内的各种细胞器中。在这里，我们展示了遗传性痉挛截瘫蛋白M1 Spastin，一种在LDS上发现的膜结合的AAA ATPase，通过两个相互关联的机制协调脂肪酸(FA)从LDS到过氧化体的运输。首先，M1 Spastin与过氧化体ABCD1形成系链复合体，促进LD-Peroxisome接触的形成。其次，M1 Spastin通过其MIT结构域将塑造膜的ESCRT-III蛋白IST1和CHMP1B招募到LDS，以促进LD到过氧化物酶体FA的转运，这可能是通过依赖于IST1和CHMP1B的LD膜形态修饰。此外，需要M1 Spastin介导的LD到过氧化酶体FA的转运来减轻LDS的脂质过氧化。M1 Spastin在将LDS与过氧化体捆绑在一起，以及将ESCRT-III组分招募到LD-Peroxisome接触部位进行FA运输方面的双重作用，可能是LDS和过氧体FA代谢缺陷相关疾病的基础。
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 interrelated 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-dependent modifications in LD membrane morphology. Furthermore, LD-to-peroxisome FA trafficking mediated by M1 Spastin is required to relieve LDs of lipid peroxidation. M1 Spastin's dual roles in tethering LDs to peroxisomes and in recruiting ESCRT-III components to LD-peroxisome contact sites for FA trafficking may underlie the pathogenesis of diseases associated with defective FA metabolism in LDs and peroxisomes.