The vacuole/lysosome is required for cell-cycle progression.
The vacuole/lysosome is required for cell-cycle progression.
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DOI：
10.7554/elife.08160
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发表时间：
2015-08-31
期刊：
影响因子：
7.7
通讯作者：
Weisman LS
中科院分区：
文献类型：
--
作者：
Jin Y;Weisman LS
细胞器通过遗传途径分配给子细胞。然而，目前尚不清楚是否存在超越遗传的机制来确保细胞器存在于所有细胞中。在这里，我们提出了一个意想不到的发现，即酵母液泡在细胞周期的启动中起着积极的重要作用。当继承失败时，就会产生新的液泡。我们证明这发生在下一个细胞周期之前，并深入了解这一替代途径。此外，我们发现遗传缺陷与液泡生物发生的急性阻断相结合，导致功能性液泡的丧失和细胞在早期 G1 期的特异性停滞。此外，液泡在细胞周期进展中的作用需要完整的 TORC1-SCH9 通路，该通路只能从成熟的液泡发出信号。这些机制可以作为液泡/溶酶体存在的检查点。 DOI：http://dx.doi.org/10.7554/eLife.08160.001 动物、真菌和其他真核生物的细胞被分为称为细胞器的子区室。每种类型的细胞器都有特定的用途，这对细胞的生命至关重要。酵母细胞有一个称为液泡的大细胞器。液泡内部呈酸性，含有可以分解其他分子的酶。先前的研究表明，当出芽酵母细胞出芽产生新的子细胞时，有一个过程确保母体的一些液泡转移到其子细胞中。然而，未能继承部分母体液泡的酵母突变体仍然可以生存。这是因为“替代”机制允许新形成的子体从头开始生成自己的液泡。金和韦斯曼现在出人意料地表明，在新的液泡形成之前，新的子细胞不能成为母细胞。实验使用了“遗传”机制有缺陷的酵母突变体，以及遗传和替代机制都有缺陷的双突变体。实验还表明，在酵母细胞的细胞核开始导致细胞分裂的事件循环之前，需要来自液泡的信号。 Jin 和 Weisman 认为，这种新发现的液泡和细胞核之间的通讯可能有助于确保所有细胞中都存在关键的细胞器。尽管目前尚不清楚为什么酵母液泡对于细胞分裂至关重要，但这些发现表明哺乳动物溶酶体（与酵母液泡相似）可能在哺乳动物中发挥类似的关键作用。如果是这种情况，那么了解这些细胞器如何与细胞核通讯可能会为如何预防肿瘤和癌症不受控制的生长提供新的见解。 DOI：http://dx.doi.org/10.7554/eLife.08160.002
Organelles are distributed to daughter cells, via inheritance pathways. However, it is unclear whether there are mechanisms beyond inheritance, which ensure that organelles are present in all cells. Here we present the unexpected finding that the yeast vacuole plays a positive essential role in initiation of the cell-cycle. When inheritance fails, a new vacuole is generated. We show that this occurs prior to the next cell-cycle, and gain insight into this alternative pathway. Moreover, we find that a combination of a defect in inheritance with an acute block in the vacuole biogenesis results in the loss of a functional vacuole and a specific arrest of cells in early G1 phase. Furthermore, this role for the vacuole in cell-cycle progression requires an intact TORC1-SCH9 pathway that can only signal from a mature vacuole. These mechanisms may serve as a checkpoint for the presence of the vacuole/lysosome. DOI: http://dx.doi.org/10.7554/eLife.08160.001 Animals, fungi and other eukaryotes have cells that are divided into sub-compartments that are called organelles. Each type of organelle serves a specific purpose that is essential for the life of the cell. Yeast cells have a large organelle called a vacuole; the inside of the vacuole is acidic and contains enzymes that can break down other molecules. Previous studies have shown that when a budding yeast cell buds to produce a new daughter cell, a process ensures that some of the mother's vacuole is transferred to its daughter. However, yeast mutants that fail to inherit some of their mother's vacuole can still survive. This is because an ‘alternative’ mechanism allows the newly forming daughter to generate its own vacuole from scratch. Jin and Weisman now unexpectedly show that a new daughter cell cannot become a mother cell until its new vacuole is formed. The experiments made use of yeast mutants that were defective in the ‘inheritance’ mechanism, and double mutants that were defective in both the inheritance and alternative mechanisms. The experiments also revealed that a signal from the vacuole is required before the yeast cell's nucleus can start the cycle of events that lead to the cell dividing. Jin and Weisman suggest that this newly identified communication between the vacuole and the nucleus may help to ensure that critical organelles are present in all cells. Though it remains unclear why the yeast vacuole is critical for a cell to divide, these findings suggest that the mammalian lysosome (which is similar to the yeast vacuole) may perform a similar critical role in mammals. If this is the case, then understanding how these organelles communicate with the nucleus may provide new insights into how to prevent the uncontrolled growth of tumors and cancer. DOI: http://dx.doi.org/10.7554/eLife.08160.002