Beclin 1 deficiency causes hepatic cell apoptosis via endoplasmic reticulum stress in zebrafish larvae
Beclin 1 deficiency causes hepatic cell apoptosis via endoplasmic reticulum stress in zebrafish larvae
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DOI：
10.1002/1873-3468.13712
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发表时间：
2020-04-01
期刊：
影响因子：
3.5
通讯作者：
Huang, Honghui
中科院分区：
文献类型：
--
作者：
Dong, Guoping;Zhang, Zhe;Huang, Honghui
Beclin 1/Atg6是一种重要的自噬基因，该基因在生物体中的缺失会导致自噬通量的降低，通常伴随着细胞的凋亡，但引起细胞凋亡的机制尚不清楚。在这里，我们敲除了斑马鱼中的beclin 1基因，并发现自噬通量在突变体中被破坏。Beclin 1基因缺失的斑马鱼在胚胎发育过程中存活，但在幼体阶段死亡。我们在突变幼虫体内发现蛋白质聚集和强烈的细胞凋亡，主要是在肝脏。突变体的肝细胞凋亡是内质网(ER)应激反应的结果，但它不是突变幼虫致死的主要原因。我们的工作认为，内质网应激诱导Beclin 1基因缺陷生物的细胞凋亡。
Beclin 1/Atg6 is an essential autophagy gene, and deficiency of this gene in organisms leads to impaired autophagic flux, usually with cell apoptosis; however, the causative mechanism of cell apoptosis is not clear. Here, we knocked out the beclin 1 gene in zebrafish and found that autophagic flux is disrupted in mutants. Beclin 1-deficient zebrafish live through embryogenesis but die at larval stage. We found accumulated protein aggregates and vigorous apoptosis in mutant larvae, predominantly in the liver. The hepatic cell apoptosis in mutants results from an endoplasmic reticulum (ER) stress response; however, it is not the leading cause of mutant larval lethality. Our work proposes that ER stress induces cell apoptosis in Beclin 1-deficient organisms.