The PITT pathway: Keeping lysosomes young.
The PITT pathway: Keeping lysosomes young.
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DOI：
10.1002/ctm2.1097
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发表时间：
2022-10
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
溶酶体是20世纪50年代由Christian de Duve发现的动物细胞中必不可少的亚细胞器。携带许多水解酶，溶酶体不仅控制营养循环和细胞生长，而且还介导各种细胞应激源的适当处理，包括病原体和受损大分子如蛋白质聚集体的清除。由于许多重要的功能依赖于一种类型的细胞器，当溶酶体受损时，它会产生疾病的风险。已知溶酶体功能障碍与衰老和许多疾病如神经退行性疾病和心血管疾病相关，通常表现为受损溶酶体的扩张和水解活性降低。2溶酶体相关疾病的标志是溶酶体膜透化（LMP）。考虑到溶酶体完整性受损的有害后果以及疾病和正常衰老中LMP的高频率，2动物细胞必须进化出快速修复受损溶酶体的基本机制。三种不同的溶酶体质量控制途径以前已被报道（图1）包括（1）转录因子EB（TFEB）途径，其响应于溶酶体损伤上调溶酶体生物发生，3（2）作为间接溶酶体修复机制的噬血作用，其通过自噬去除受损的溶酶体，4，5，6和（3）用于直接和快速修复小的溶酶体膜孔的转运所需的内体分选复合物（ESCRT）途径。7-9虽然TFEB和噬菌体在用新的溶酶体替换受损的溶酶体方面很重要，但它们可能无法迅速响应以阻断急性溶酶体损伤。
Lysosomes are essential subcellular organelles in animal cells discovered by Christian de Duve in 1950s. Carrying many hydrolytic enzymes, lysosomes not only control nutrient recycling and cellular growth, but also mediate the proper handling of various cellular stressors, including the clearance of pathogens and damaged macromolecules like protein aggregates. 1 With many important functions dependent on one type of organelle, it creates the risk of developing diseases when lysosomes are compromised. Lysosomal dysfunction is known to be associated with aging and many diseases such as neurodegenerative and cardiovascular diseases, usually exhibited as expansion of compromised lysosomes with reduced hydrolytic activity. 2 A hallmark of lysosomal-related diseases is lysosomal membrane permeabilization (LMP). Given the detrimental consequences of impaired lysosomal integrity and the high frequency of LMP in diseases and normal aging, 2 animal cells must have evolved essential mechanisms to rapidly repair damaged lysosomes. Three distinct lysosomal quality control pathways have been previously reported (Figure 1) including (1) the transcription factor EB (TFEB) pathway that upregulates lysosomal biogenesis in response to lysosomal damage, 3 (2) lysophagy as an indirect lysosomal repair mechanism that removes damaged lysosomes through autophagy, 4, 5, 6 and (3) the endosomal sorting complex required for transport (ESCRT) pathway for direct and rapid repair of small lysosomal membrane pores. 7-9 While TFEB and lysophagy are important in replacing damaged lysosomes with new ones, they likely are unable to respond rapidly enough to block acute lyso-
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影响因子：
18.2
作者：
Xu H;Ren D
通讯作者：
Ren D
DOI：
10.1126/science.aar5078
发表时间：
2018-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Skowyra ML;Schlesinger PH;Naismith TV;Hanson PI
通讯作者：
Hanson PI
影响因子：
6.7
作者：
Lopez-Jimenez, Ana T.;Cardenal-Munoz, Elena;Soldati, Thierry
通讯作者：
Soldati, Thierry
影响因子：
29
作者：
Gibbons GS;Lee VMY;Trojanowski JQ
通讯作者：
Trojanowski JQ
影响因子：
16.6
作者：
Niekamp P;Scharte F;Sokoya T;Vittadello L;Kim Y;Deng Y;Südhoff E;Hilderink A;Imlau M;Clarke CJ;Hensel M;Burd CG;Holthuis JCM
通讯作者：
Holthuis JCM