Zhang Yong, Qi Haiyan, Taylor Robert, Xu Weihong, Liu Leroy F, Jin Shengkan
Pharmacology Department and the Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Autophagy. 2007 Jul-Aug;3(4):337-46. doi: 10.4161/auto.4127. Epub 2007 Jul 9.
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 forthese 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 atgmutant strains, atg1delta, atg6delta, atg8delta and atg12delta, 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.
自噬是一种依赖溶酶体的细胞降解过程。携带必需自噬基因缺失的生物体表现出各种病理状况，包括哺乳动物中的癌症和秀丽隐杆线虫寿命缩短。这些表型的直接原因尚不清楚。在这里，我们以酵母为模型系统来表征自噬相关（ATG）基因缺失的细胞后果。我们发现，atg突变株atg1delta、atg6delta、atg8delta和atg12delta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无法降解线粒体。在需要线粒体氧化磷酸化才能存活的非发酵培养基中，这些atg菌株表现出生长缺陷，细胞周期的G(1)期细胞群体增加。这些细胞的耗氧率较低，线粒体电子传递链活性降低。在这些生长条件下，atg菌株的线粒体膜电位较低。此外，这些突变体产生更高水平的活性氧（ROS），并且它们易于积累功能失调的线粒体。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影响，并表明自噬在线粒体维持中起关键作用。
