Triggered recruitment of ESCRT machinery promotes endolysosomal repair.

Triggered recruitment of ESCRT machinery promotes endolysosomal repair.
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DOI:
10.1126/science.aar5078
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发表时间:
2018-04-06
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Hanson PI
Hanson PI
中科院分区:
其他
文献类型:
--
作者:
Skowyra ML;Schlesinger PH;Naismith TV;Hanson PI

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内溶酶体可被多种物质破坏。终末受损的隔间被lysophagy降解,但修复可挽救的细胞器的途径知之甚少。在这里,我们发现,内体分选复合物所需的运输(ESCRT)机制,已知介导出芽和分裂的内溶酶体,也发挥了重要作用,在他们的修复。ESCRT通过一种需要钙和ESCRT激活因子的途径被迅速募集到急性损伤的内溶酶体中,这种途径不依赖于噬菌体。我们使用活细胞成像来证明ESCRT对内溶酶体膜中的小穿孔做出反应,并使隔室能够从有限的损伤中恢复。破坏内溶酶体的二氧化硅晶体也触发ESCRT募集。因此,ESCRT提供了一种防御内溶酶体损伤可能是相关的生理和病理背景。受损的内体和溶酶体迅速招募ESCRT机制,以促进膜修复。
Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the Endosomal Sorting Complex Required for Transport (ESCRT) machinery, known to mediate budding and fission on endolysosomes, also plays an essential role in their repair. ESCRTs were rapidly recruited to acutely injured endolysosomes via a pathway requiring calcium and ESCRT-activating factors that was independent of lysophagy. We used live cell imaging to demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts. Damaged endosomes and lysosomes rapidly recruit ESCRT machinery to promote membrane repair.
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