The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity.
The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity.
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DOI：
10.1083/jcb.201602090
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发表时间：
2016-10-24
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Li Y;Chen B;Zou W;Wang X;Wu Y;Zhao D;Sun Y;Liu Y;Chen L;Miao L;Yang C;Wang X
保持溶酶体膜稳定性的机制和决定因素尚不清楚。在这里，李等人。研究表明，溶酶体膜蛋白 SCAV-3（人类 LIMP-2 的秀丽隐杆线虫同源物）是溶酶体完整性和正常成人寿命的关键调节因子。溶酶体降解大分子并回收代谢物，并参与调节细胞稳态的多种过程。溶酶体受到单个磷脂双层的限制，该双层形成屏障，将有效的管腔水解酶与其他细胞成分分开，从而保护后者免受不必要的降解。维持溶酶体膜完整性的机制仍然未知。在这里，我们确定了 SCAV-3（人类 LIMP-2 的秀丽隐杆线虫同源物）是溶酶体完整性、运动性和动力学的关键调节因子。 scav-3的缺失导致溶酶体膜破裂并显着缩短寿命。这两种表型都被 LMP-1 或 LMP-2（线虫 LAMP）的增强表达所抑制，表明长寿需要维持溶酶体完整性。值得注意的是，胰岛素/胰岛素样生长因子 1 (IGF-1) 信号传导的减少可抑制溶酶体损伤，并以 DAF-16 依赖性方式延长 scav-3(lf) 动物的寿命。我们的数据表明，SCAV-3 对于保持溶酶体膜稳定性至关重要，并且胰岛素/IGF-1 信号通路对溶酶体完整性的调节会影响寿命。
The mechanisms and determinants preserving lysosomal membrane stability are unclear. Here, Li et al. show that the lysosomal membrane protein SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, is a key regulator of lysosome integrity and normal adult lifespan. Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16–dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity.
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影响因子：
6.2
作者：
Anisimov, Vladimir N.;Bartke, Andrzej
通讯作者：
Bartke, Andrzej
溶酶体膜的糖蛋白。
影响因子：
7.8
作者：
LEWIS, V;GREEN, SA;MARSH, M;VIHKO, P;HELENIUS, A;MELLMAN, I
通讯作者：
MELLMAN, I
影响因子：
3.8
作者：
Gonzalez, Ashley;Valeiras, Mark;Sidransky, Ellen;Tayebi, Nahid
通讯作者：
Tayebi, Nahid
影响因子：
64.8
作者：
Calfon, M;Zeng, HQ;Ron, D
通讯作者：
Ron, D
影响因子：
4.5
作者：
Hansen M;Hsu AL;Dillin A;Kenyon C
通讯作者：
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