title: The Ccz1 mediates the autophagic clearance of damaged mitochondria in response to oxidative stress in Candida albicans.
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 ccz1Δ/Δ 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 ccz1Δ/Δ 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 ccz1Δ/Δ 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.
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: dongyijie8837@163.com.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: yuqilin7007@163.com.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: 13820602275@163.com.
authors.forename: Yulu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, PR China. Electronic address: nkskyxn@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: zhaoqiang@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: jiashang0802@163.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Jia
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: zhangbing0712@yeah.net.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: zk2009zf@126.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin, PR China. Electronic address: zhangbiao6853@126.com.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: xinglaij@163.com.
authors.forename: Laijun
authors.initials: L
authors.lastname: Xing
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin, PR China. Electronic address: nklimingchun@163.com.
authors.forename: Mingchun
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D001343:Autophagy; D002176:Candida albicans / Q000378:metabolism*; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology; D002478:Cells, Cultured; D005260:Female; D005656:Fungal Proteins / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology / Q000502:physiology; D053078:Membrane Potential, Mitochondrial; D008813:Mice, Inbred ICR; D050296:Microbial Viability; D018384:Oxidative Stress; D010587:Phagocytosis; D033921:Vesicular Transport Proteins / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D033921:Vesicular Transport Proteins
keywords: Autophagy; Candida albicans; Ccz1; Oxidative stress; Virulence