Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process.
Xindi GaoYi FuShengyi SunTingyi GuYanjian LiTianshu SunHailong LiWei DuChenhao SuoChao LiYiru GaoYang MengYue NiSheng YangTian LanSixiang SaiJun-Fang TengKun YuPing WangChen DingPublished in: Nature communications (2022)
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.
Keyphrases
- dna binding
- heat shock
- reactive oxygen species
- dna damage
- oxidative stress
- transcription factor
- poor prognosis
- quality control
- binding protein
- electron transfer
- induced apoptosis
- cell death
- heat stress
- endoplasmic reticulum stress
- endoplasmic reticulum
- cell cycle arrest
- single cell
- long non coding rna
- protein protein
- dna methylation
- gene expression
- cell proliferation
- signaling pathway
- drug delivery
- nitric oxide
- mouse model
- fluorescent probe