title: Candida albicans autophagy, no longer a bystander: Its role in tolerance to ER stress-related antifungal drugs.
abstract: Autophagy is a degradation process involved in pathogenicity of many pathogenic fungi. However, its roles in Candida albicans, the leading fungal pathogen in human beings, remain to be detailed. Most recently, we found that endoplasmic reticulum (ER) stress-inducing conditions led to transcriptional up-regulation of C. albicans autophagy-related (ATG) genes, implying a possible link between autophagy and ER stress response in this pathogen. Using a series of C. albicans ATG mutants and autophagy reporting systems, we found that both treatment of ER stress-related drugs and loss of the ER calcium pump Spf1 promoted autophagic flux of Atg8 and Lap41 (a homologue of Saccharomyces cerevisiae Ape1), indicating that these conditions induce autophagy. Moreover, deletion of ATG genes in the spf1Δ/Δ mutant rendered cells hypersensitive to these drugs and caused activation of UPR, revealing a role of autophagy in alleviating ER stress. In addition, only treatment of tunicamycin and loss of Spf1 in combination increased autophagic flux of the ER component Sec63, suggesting that most of the ER stress-related conditions cause non-selective autophagy rather than selective ER phagy. This study uncovers the important role of C. albicans autophagy in ER stress response and tolerance to antifungal drugs.
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Jia
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Chenpeng
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Yulu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China; Nankai Univ, TEDA, TEDA Sch Biol Sci & Biotechnol, Tianjin 300071, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tianjin Traditional Chinese Medicine University, Tianjin 300193, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071, PR China. Electronic address: nklimingchun@163.com.
authors.forename: Mingchun
authors.initials: M
authors.lastname: Li
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism*; D001343:Autophagy; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D017353:Gene Deletion; D012441:Saccharomyces cerevisiae
chemical_list: D000935:Antifungal Agents
keywords: Antifungal drug; Autophagy; Candida albicans; ER phagy; ER stress; Spf1