细胞生物学
线粒体
生物
细胞器
活性氧
柠檬酸循环
线粒体DNA
新生隐球菌
基因
生物化学
遗传学
新陈代谢
作者
Xindi Gao,Yi Fu,Shengyi Sun,Tingyi Gu,Yanjian Li,Tianshu Sun,Hailong Li,Wei Du,Chenhao Suo,Chao Li,Yiru Gao,Meng Yang,Yue Ni,Sheng Yang,Tian Lan,Sixiang Sai,Jiayi Li,Kun Yu,Ping Wang,Chen Ding
标识
DOI:10.1038/s41467-022-33168-1
摘要
Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.
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