The entry of unclosed autophagosomes into vacuoles and its physiological relevance.
The entry of unclosed autophagosomes into vacuoles and its physiological relevance.
复制标题
未封闭的自噬体进入液泡及其生理相关性
DOI：
10.1371/journal.pgen.1010431
复制
发表时间：
2022-10
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
文献中广泛指出，在大自噬/自噬期间，闭合的成熟自噬体（AP）与溶酶体/空泡融合。以前，我们发现，未关闭的AP积累的Vps 21/Rab 5和ESCRT突变体的液泡外集群后，一个短时期的氮饥饿。然而，这些未关闭的AP的命运仍然不清楚。在这项研究中，我们使用了细胞和生物化学的方法相结合，以表明，不封闭的双膜AP进入空泡，并形成不封闭的单膜自噬体后，长时间的氮饥饿或雷帕霉素治疗。在Vps 21突变细胞中，非封闭双膜AP进入液泡的过程中，均涉及到胞内水解酶、液泡转运伴侣蛋白（VTC）、Ypt 7和Vam 3。液泡水解酶Pep 4或Prb 1的过表达或大多数VTC蛋白的耗尽促进未闭合的AP进入Vps 21突变细胞的液泡，而Pep 4和/或Prb 1的耗尽则延迟进入液泡。与典型自噬突变体的二倍体细胞完全不育相反，Vps 21突变体的二倍体细胞通过减数分裂到孢子形成，受益于长时间氮饥饿后未关闭的AP进入液泡。总的来说，这些数据代表了一个新的观察结果，即未闭合的双膜AP可以在长时间的自噬诱导后进入空泡，最有可能作为一种生存策略。
It is widely stated in the literature that closed mature autophagosomes (APs) fuse with lysosomes/vacuoles during macroautophagy/autophagy. Previously, we showed that unclosed APs accumulated as clusters outside vacuoles in Vps21/Rab5 and ESCRT mutants after a short period of nitrogen starvation. However, the fate of such unclosed APs remains unclear. In this study, we used a combination of cellular and biochemical approaches to show that unclosed double-membrane APs entered vacuoles and formed unclosed single-membrane autophagic bodies after prolonged nitrogen starvation or rapamycin treatment. Vacuolar hydrolases, vacuolar transport chaperon (VTC) proteins, Ypt7, and Vam3 were all involved in the entry of unclosed double-membrane APs into vacuoles in Vps21-mutant cells. Overexpression of the vacuolar hydrolases, Pep4 or Prb1, or depletion of most VTC proteins promoted the entry of unclosed APs into vacuoles in Vps21-mutant cells, whereas depletion of Pep4 and/or Prb1 delayed the entry into vacuoles. In contrast to the complete infertility of diploid cells of typical autophagy mutants, diploid cells of Vps21 mutant progressed through meiosis to sporulation, benefiting from the entry of unclosed APs into vacuoles after prolonged nitrogen starvation. Overall, these data represent a new observation that unclosed double-membrane APs can enter vacuoles after prolonged autophagy induction, most likely as a survival strategy.
登录
查看更多内容
多特异性语法同源物，VAM3P，对于自噬和生物合成蛋白传输到液泡必不可少。
影响因子：
7.8
作者：
Darsow, T;Rieder, SE;Emr, SD
通讯作者：
Emr, SD
巨自噬不需要酵母磷脂酶 D、Spo14
影响因子：
2.6
作者：
Chen, Yun;Wu, Zulin;Liang, Yongheng
通讯作者：
Liang, Yongheng
DOI：
10.1016/0167-4781(83)90019-2
发表时间：
1983-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
DISTEL, B;AL, EJM;JONES, EW
通讯作者：
JONES, EW
DOI：
10.1016/0005-2744(78)90253-x
发表时间：
1978-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FREY, J;ROHM, KH
通讯作者：
ROHM, KH
影响因子：
4.8
作者：
Noda, T;Ohsumi, Y
通讯作者：
Ohsumi, Y