Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process

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.

Fu, YiNortheastern University (författare)
Sun, ShengyiNortheastern University (författare)
Gu, TingyiNortheastern University (författare)
Li, YanjianNortheastern University (författare)
Sun, TianshuPeking Union Medical College (författare)
Li, HailongChina Medical University, Shenyang (författare)
Du, WeiNortheastern University (författare)
Suo, ChenhaoNortheastern University (författare)
Li, ChaoNortheastern University (författare)
Gao, YiruNortheastern University (författare)
Meng, YangNortheastern University (författare)
Ni, YueNortheastern University (författare)
Yang, ShengNortheastern University (författare)
Lan, TianNortheastern University (författare)
Sai, SixiangBinzhou Medical University (författare)
Li, JiayiLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups(Swepub:lu)mphy-jli (författare)
Yu, KunNortheastern University (författare)
Wang, PingLouisiana State University Health Sciences Center (författare)
Ding, ChenNortheastern University (författare)
Northeastern UniversityPeking Union Medical College (creator_code:org_t)

Ingår i:Nature Communications: Springer Science and Business Media LLC13:12041-1723

Av författaren/redakt...: Gao, Xindi; Fu, Yi; Sun, Shengyi; Gu, Tingyi; Li, Yanjian; Sun, Tianshu; visa fler...; Li, Hailong; Du, Wei; Suo, Chenhao; Li, Chao; Gao, Yiru; Meng, Yang; Ni, Yue; Yang, Sheng; Lan, Tian; Sai, Sixiang; Li, Jiayi; Yu, Kun; Wang, Ping; Ding, Chen; visa färre...

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