Niemann-Pick type C proteins promote microautophagy by expanding raft-like membrane domains in the yeast vacuole
Niemann-Pick type C proteins promote microautophagy by expanding raft-like membrane domains in the yeast vacuole
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DOI：
10.7554/elife.25960
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发表时间：
2017-06-07
期刊：
影响因子：
7.7
通讯作者：
Fujimoto, Toyoshi
中科院分区：
文献类型：
--
作者：
Tsuji, Takuma;Fujimoto, Megumi;Fujimoto, Toyoshi
C型尼曼匹克病是由NPC蛋白功能障碍引起的胆固醇储存病，NPC蛋白将胆固醇从溶酶体腔转运到该隔室的界膜。使用冷冻断裂电子显微镜，我们在这里表明，酵母NPC的直系同源物，Ncr1p和Npc2p，是必不可少的形成和扩大筏状结构域的空泡（溶酶体）膜，无论是在静止期和急性氮饥饿。此外，扩大筏状结构域吞噬脂滴的微自噬机制。我们还发现，多泡体途径在急性氮饥饿中通过将固醇递送到液泡中在微自噬中起着至关重要的作用。这些数据表明，NPC蛋白在稳定期和氮饥饿条件下促进微自噬，可能是通过增加液泡限制膜中的甾醇。
Niemann-Pick type C is a storage disease caused by dysfunction of NPC proteins, which transport cholesterol from the lumen of lysosomes to the limiting membrane of that compartment. Using freeze fracture electron microscopy, we show here that the yeast NPC orthologs, Ncr1p and Npc2p, are essential for formation and expansion of raft-like domains in the vacuolar (lysosome) membrane, both in stationary phase and in acute nitrogen starvation. Moreover, the expanded raft-like domains engulf lipid droplets by a microautophagic mechanism. We also found that the multivesicular body pathway plays a crucial role in microautophagy in acute nitrogen starvation by delivering sterol to the vacuole. These data show that NPC proteins promote microautophagy in stationary phase and under nitrogen starvation conditions, likely by increasing sterol in the limiting membrane of the vacuole.