自噬
白色念珠菌
肌醇
细胞生物学
白色体
DNA损伤
生物
液泡
生物化学
DNA
化学
微生物学
受体
细胞质
细胞凋亡
作者
Huan‐Feng Duan,Yixuan Dong,Hangqi Zhu,Ying Deng,Chula Sa,Qilin Yu,Mingchun Li
标识
DOI:10.1016/j.bbamcr.2023.119622
摘要
DNA damage-induced autophagy is a new type of autophagy that differs from traditional macroautophagy; however, this type of autophagy has not been identified in the pathogenic fungus Candida albicans. Inositol polyphosphates are involved in the regulation of DNA damage repair and macroautophagy; however, whether inositol polyphosphates are involved in the regulation of DNA damage-induced autophagy remains unclear. In this study, we identified DNA damage-induced autophagy in C. albicans and systematically investigated the mechanisms of inositol polyphosphate pathway regulation. We found that the core machinery of macro autophagy is also essential for DNA damage-induced autophagy, and that inositol polyphosphate synthetases Kcs1, Ipk1, and Vip1 play a critical role in autophagy. In this study, we focused on Kcs1 and Vip1, which are responsible for the synthesis of inositol pyrophosphate. The kcs1Δ/Δ and vip1Δ/Δ strains exhibited reduced number of phagophore assembly sites (PAS) and autophagic bodies. The recruitment of autophagy-related gene 1 (Atg1) to PAS was significantly affected in the kcs1Δ/Δ and vip1Δ/Δ strains. Target of rapamycin complex 1 kinase activity was elevated in kcs1Δ/Δ and vip1Δ/Δ strains, which significantly inhibited the initiation of autophagy. Atg18 Localization was altered in these mutants. The absence of Kcs1 or Vip1 caused the downregulation of RAD53, a key gene in the DNA damage response. These data provide further understanding of the mechanism of autophagy regulation in C. albicans.
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