The role of autophagy in mitochondria maintenance -: Characterization of mitochondrial functions in autophagy-deficient S-cerevisiae strains
The role of autophagy in mitochondria maintenance -: Characterization of mitochondrial functions in autophagy-deficient S-cerevisiae strains
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DOI：
10.4161/auto.4127
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发表时间：
2007-07-01
期刊：
影响因子：
13.3
通讯作者：
Jin, Shengkan
中科院分区：
文献类型：
--
作者：
Zhang, Yong;Qi, Haiyan;Jin, Shengkan
自噬是一种溶酶体依赖的细胞降解过程。携带必需的自噬基因缺失的生物体表现出各种病理状况，包括哺乳动物的癌症和C.优雅的这些表型的直接原因尚不清楚。在这里，我们使用酵母作为模型系统来表征ATG（自噬相关）基因缺失的细胞后果。我们发现atg突变株atg 1 Delta、atg 6 Delta、atg 8 Delta和atg 12 Delta表现出与线粒体生物学相关的缺陷。这些菌株在静止培养中不能降解线粒体。在需要线粒体氧化磷酸化才能生存的非发酵培养基中，这些atg菌株显示出生长缺陷，在细胞周期的G（1）期细胞数量增加。细胞耗氧率降低，线粒体电子传递链活性降低。在这些生长条件下，atg菌株具有较低的线粒体膜电位。此外，这些突变体产生更高水平的活性氧（ROS），它们容易积累功能障碍的线粒体。这项研究清楚地表明，自噬缺陷对线粒体功能的各个方面都有功能性影响，并表明自噬在线粒体维持中起着关键作用。
Autophagy is a lysosome-dependent cellular degradation process. Organisms bearing deletions of the essential autophagy genes exhibit various pathological conditions, including cancer in mammals and shortened life span in C. elegans. The direct cause for these phenotypes is not clear. Here we used yeast as a model system to characterize the cellular consequence of ATG (autophagy-related) gene deletions. We found that the atg mutant strains, atg1 Delta, atg6 Delta, atg8 Delta and atg 12 Delta, showed defects related to mitochondrial biology. These strains were unable to degrade mitochondria in stationary culture. In non-fermentable medium, which requires mitochondrial oxidative phosphorylation for survival, these atg strains showed a growth defect with an increased cell population at the G(1) phase of the cell cycle. The cells had lower oxygen consumption rates and reduced mitochondrial electron transport chain activities. Under these growth conditions, the atg strains had lower mitochondrial membrane potential. In addition, these mutants generated higher levels of reactive oxygen species (ROS) and they were prone to accumulate dysfunctional mitochondria. This study clearly indicates that an autophagy defect has a functional impact on various aspects of mitochondrial functions and suggests a critical role of autophagy in mitochondria maintenance.