Starvation induced cell death in autophagy-defective yeast mutants is caused by mitochondria dysfunction.
Starvation induced cell death in autophagy-defective yeast mutants is caused by mitochondria dysfunction.
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DOI：
10.1371/journal.pone.0017412
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发表时间：
2011-02-25
期刊：
影响因子：
3.7
通讯作者：
Ohsumi Y
中科院分区：
文献类型：
--
作者：
Suzuki SW;Onodera J;Ohsumi Y
自噬是一种高度保守的细胞降解和再循环系统，在营养饥饿期间对细胞存活至关重要。活力的丧失已被用作初步筛选来鉴定酵母酿酒酵母的自噬缺陷（atg）突变体，但这些突变体的细胞死亡机制仍不清楚。当将在丰富培养基中生长的细胞转移到合成的氮饥饿培养基中时，分泌的代谢产物将细胞外pH降低到3.0以下，并且自噬缺陷突变体大多死亡。我们发现，饥饿培养基的缓冲显著地恢复了atg突变体的生存能力。响应于饥饿，野生型（WT）细胞能够上调呼吸途径和ROS（活性氧）清除酶的组分，但atg突变体缺乏这种合成能力。因此，自噬缺陷突变体积累了高水平的ROS，导致呼吸功能缺陷，导致线粒体DNA（mtDNA）的丢失。我们还发现，mtDNA缺陷细胞在低pH饥饿条件下会发生细胞死亡。总之，在饥饿条件下，非选择性自噬，而不是线粒体自噬，在防止ROS积累，从而维持线粒体功能中起着至关重要的作用。饥饿反应的失败是atg突变体细胞死亡的主要原因。
Autophagy is a highly-conserved cellular degradation and recycling system that is essential for cell survival during nutrient starvation. The loss of viability had been used as an initial screen to identify autophagy-defective (atg) mutants of the yeast Saccharomyces cerevisiae, but the mechanism of cell death in these mutants has remained unclear. When cells grown in a rich medium were transferred to a synthetic nitrogen starvation media, secreted metabolites lowered the extracellular pH below 3.0 and autophagy-defective mutants mostly died. We found that buffering of the starvation medium dramatically restored the viability of atg mutants. In response to starvation, wild-type (WT) cells were able to upregulate components of the respiratory pathway and ROS (reactive oxygen species) scavenging enzymes, but atg mutants lacked this synthetic capacity. Consequently, autophagy-defective mutants accumulated the high level of ROS, leading to deficient respiratory function, resulting in the loss of mitochondria DNA (mtDNA). We also showed that mtDNA deficient cells are subject to cell death under low pH starvation conditions. Taken together, under starvation conditions non-selective autophagy, rather than mitophagy, plays an essential role in preventing ROS accumulation, and thus in maintaining mitochondria function. The failure of response to starvation is the major cause of cell death in atg mutants.
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影响因子：
4.5
作者：
Fabrizio P;Hoon S;Shamalnasab M;Galbani A;Wei M;Giaever G;Nislow C;Longo VD
通讯作者：
Longo VD
影响因子：
13.3
作者：
Zhang, Yong;Qi, Haiyan;Jin, Shengkan
通讯作者：
Jin, Shengkan
影响因子：
56.9
作者：
Ishikawa, Kaori;Takenaga, Keizo;Hayashi, Jun-Ichi
通讯作者：
Hayashi, Jun-Ichi
ATG32是一种线粒体蛋白，在线粒体过程中赋予了选择性。
影响因子：
11.8
作者：
Kanki, Tomotake;Wang, Ke;Cao, Yang;Baba, Misuzu;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
影响因子：
56.9
作者：
OGUR, M;JOHN, RS;NAGAI, S
通讯作者：
NAGAI, S