2. Academic Validation
  3. Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process

Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process

  • Nat Commun. 2022 Sep 15;13(1):5407. doi: 10.1038/s41467-022-33168-1.
Xindi Gao 1,  Yi Fu 1,  Shengyi Sun 1,  Tingyi Gu 1,  Yanjian Li 1,  Tianshu Sun 2 3,  Hailong Li 4,  Wei Du 1,  Chenhao Suo 1,  Chao Li 1,  Yiru Gao 1,  Yang Meng 1,  Yue Ni 1,  Sheng Yang 1,  Tian Lan 1,  Sixiang Sai 5,  Jiayi Li 6,  Kun Yu 7,  Ping Wang 8,  Chen Ding 9
Affiliations

Affiliations

  • 1 College of Life and Health Sciences, Northeastern University, 110819, Shenyang, Liaoning, China.
  • 2 Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, 100730, Beijing, China.
  • 3 Department of Scientific Research, Central Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Science, 100730, Beijing, China.
  • 4 NHC Key Laboratory of AIDS Immunology, National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, 110001, Shenyang, China.
  • 5 School of Medicine, Binzhou Medical University, 264003, Yantai, China.
  • 6 Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Lund University, BMC A10, 22184, Lund, Sweden.
  • 7 College of Medicine and Biological Information Engineering, Northeastern University, 110169, Shenyang, China.
  • 8 Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
  • 9 College of Life and Health Sciences, Northeastern University, 110819, Shenyang, Liaoning, China. dingchen@mail.neu.edu.cn.
PMID: 36109512 DOI: 10.1038/s41467-022-33168-1
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 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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