Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans.
Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans.
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DOI：
10.1083/jcb.200511103
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发表时间：
2006-04-24
期刊：
影响因子：
--
通讯作者：
Tavernarakis N
中科院分区：
文献类型：
--
作者：
Artal-Sanz M;Samara C;Syntichaki P;Tavernarakis N
坏死性细胞死亡是由垂死细胞所表现出的独特形态特征来定义的（Walker, N.I., B.V. Harmon, G.C. Gobe, and J.F. Kerr. 1988.Methods Achiev. Exp. Pathol. 13:18–54）。人们对坏死过程中发生的产生这些坏死特征的细胞事件知之甚少。最近对线虫秀丽隐杆线虫的研究表明，细胞质酸化在坏死过程中发生，并且是细胞死亡所必需的（Syntichaki, P., C. Samara, and N. Tavernarakis. 2005. Curr. Biol. 15:1249–1254）。然而，细胞质酸化的起源仍然难以捉摸。我们发现内体和溶酶体区室的碱化可改善由不同刺激引发的坏死性细胞死亡。此外，导致溶酶体生物发生和功能改变的基因突变显着影响神经元坏死。我们使用基因编码的荧光标记来追踪体内神经变性过程中溶酶体的命运。引人注目的是，我们发现溶酶体融合并仅定位在肿胀的细胞核周围。在细胞死亡的后期，细胞核凝结并向细胞外围迁移，而绿色荧光蛋白标记的溶酶体膜褪色，表明溶酶体破裂。我们的研究结果表明，溶酶体在坏死细胞死亡过程中的细胞破坏中发挥着重要作用，这在后生动物中可能是保守的。
Necrotic cell death is defined by distinctive morphological characteristics that are displayed by dying cells (Walker, N.I., B.V. Harmon, G.C. Gobe, and J.F. Kerr. 1988. Methods Achiev. Exp. Pathol. 13:18–54). The cellular events that transpire during necrosis to generate these necrotic traits are poorly understood. Recent studies in the nematode Caenorhabditis elegans show that cytoplasmic acidification develops during necrosis and is required for cell death (Syntichaki, P., C. Samara, and N. Tavernarakis. 2005. Curr. Biol. 15:1249–1254). However, the origin of cytoplasmic acidification remains elusive. We show that the alkalization of endosomal and lysosomal compartments ameliorates necrotic cell death triggered by diverse stimuli. In addition, mutations in genes that result in altered lysosomal biogenesis and function markedly affect neuronal necrosis. We used a genetically encoded fluorescent marker to follow lysosome fate during neurodegeneration in vivo. Strikingly, we found that lysosomes fuse and localize exclusively around a swollen nucleus. In the advanced stages of cell death, the nucleus condenses and migrates toward the periphery of the cell, whereas green fluorescent protein–labeled lysosomal membranes fade, indicating lysosomal rupture. Our findings demonstrate a prominent role for lysosomes in cellular destruction during necrotic cell death, which is likely conserved in metazoans.
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DOI：
10.1083/jcb.102.5.1593
发表时间：
1986-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lippincott-Schwartz J;Fambrough DM
通讯作者：
Fambrough DM
影响因子：
4.8
作者：
Nehrke, K;Melvin, JE
通讯作者：
Melvin, JE
影响因子：
3.3
作者：
Hermann, GJ;Schroeder, LK;Priess, JR
通讯作者：
Priess, JR
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
3.5
作者：
Li, JZ;Vawter, MP;Myers, RM
通讯作者：
Myers, RM