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Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process

Gao, Xindi ; Fu, Yi ; Sun, Shengyi ; Gu, Tingyi ; Li, Yanjian ; Sun, Tianshu ; Li, Hailong ; Du, Wei ; Suo, Chenhao and Li, Chao , et al. (2022) In Nature Communications 13(1).
Abstract

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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
13
issue
1
article number
5407
publisher
Nature Publishing Group
external identifiers
  • pmid:36109512
  • scopus:85137897416
ISSN
2041-1723
DOI
10.1038/s41467-022-33168-1
language
English
LU publication?
yes
id
5f387dec-f66e-4f4e-adc8-95ad8af8db1f
date added to LUP
2022-12-01 08:40:28
date last changed
2024-04-18 05:25:06
@article{5f387dec-f66e-4f4e-adc8-95ad8af8db1f,
  abstract     = {{<p>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.</p>}},
  author       = {{Gao, Xindi and Fu, Yi and Sun, Shengyi and Gu, Tingyi and Li, Yanjian and Sun, Tianshu and Li, Hailong and Du, Wei and Suo, Chenhao and Li, Chao and Gao, Yiru and Meng, Yang and Ni, Yue and Yang, Sheng and Lan, Tian and Sai, Sixiang and Li, Jiayi and Yu, Kun and Wang, Ping and Ding, Chen}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process}},
  url          = {{http://dx.doi.org/10.1038/s41467-022-33168-1}},
  doi          = {{10.1038/s41467-022-33168-1}},
  volume       = {{13}},
  year         = {{2022}},
}