Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8322451 | The International Journal of Biochemistry & Cell Biology | 2015 | 11 Pages |
Abstract
Autophagy plays a critical role in response to numerous cellular stresses, such as nutrient deprivation, hypoxia, starvation and organelle damage. The disruption of autophagy pathway affects multiple aspects of cellular stress response. Here we for the first time identified Ccz1 as an essential component for autophagy in Candida albicans. Our experiments demonstrated that loss of CCZ1 gene led to vacuolar fragmentation and disruption of the autophagy pathway. Our results also suggested that Ccz1 functioned in oxidative stress. In the ccz1Î/Î mutant, the levels of reactive oxidative species (ROS) sharply increased under H2O2 treatment. Further studies demonstrated that breakdown of the autophagic clearance pathway led to the accumulation of oxidative stress-damaged mitochondria, and consequently elevated cellular ROS levels in the ccz1Î/Î mutant. Furthermore, deletion of CCZ1 led to a significant defect in filamentous development at both 30 °C and 37 °C. The disruption of CCZ1 gene led to decreased capacity of macrophage killing and increased sensitivity to the macrophages. In addition, the ccz1Î/Î mutant exhibited attenuated virulence and decreased fungal burdens in the mouse systemic infection model, indicating that CCZ1 might provide a promising target for antifungal drugs development. In summary, our findings provide new insights into the understanding of autophagy-related gene in C. albicans.
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Authors
Yijie Dong, Qilin Yu, Yulu Chen, Ning Xu, Qiang Zhao, Chang Jia, Bing Zhang, Kai Zhang, Biao Zhang, Laijun Xing, Mingchun Li,