Thioredoxin-dependent regulation of AIF-mediated DNA damage |
| |
| Affiliation: | 1. Department of Pharmacy, Faculty of Science, National University of Singapore, S117543, Republic ofSingapore;2. Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A⁎STAR), S138648, Republic of Singapore;3. Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77, Stockholm, Sweden;4. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, S117597, Republic of Singapore;1. Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan;2. Laboratory of Chemical Biology, Advanced Medicinal Research Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530, Japan;3. Department of Thoracic Oncology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan;1. Metabolic Biophysics, Professional Toxicology and Applied Environmental Laboratory, Department of Biophysics, Medicine Faculty of Sousse, Sousse University, Sousse 4002, Tunisia;2. Laboratory of Natural Substances, National Institute of Research and Physical–Chemical Analysis (INRAP), Technopole Sidi Thabet 2020, Tunisia;3. Neurology Department of Central Hospital University (CHU), Sousse University, Sousse 4002, Tunisia;1. Institute of Cardiovascular Physiopathology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, Argentina;2. Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET), Faculty of Medicine, Argentina;3. Institute of Biochemistry and Molecular Medicine (IBIMOL UBA-CONICET), School of Pharmacy and Biochemistry; University of Buenos Aires, Buenos Aires, Argentina;1. Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, Peoples Republic of China;2. Laboratory of Transplantation and Immunology, Xuzhou Medical College, Xuzhou, Jiangsu, Peoples Republic of China |
| |
| Abstract: | The thioredoxin (Trx) system is one major redox system in mammalian cells. One of its component, Trx, is involved in redox homeostasis and many cellular biological processes through participating in disulfide reduction, S-nitrosylation/S-denitrosylation reactions and protein-protein interactions. In this study, we report the identification of a novel interaction between cytosolic/nuclear Trx1 and apoptosis inducing factor (AIF), and the redox sensitivity and biological significance of the Trx-AIF interaction was characterized. Cytosolic Trx1 but not mitochondrial Trx2 was observed to interact with AIF under physiological conditions and Trx1's active site cysteines were crucial for the interaction. Under oxidative stress conditions, Trx-AIF interaction was disrupted. When the treated cells were allowed to recover from oxidative stress by means of removal of the oxidants, interaction between Trx1 and AIF was re-established time-dependently, which underpins the biological relevance of a Trx-dependent redox regulation of AIF-mediated cell death. Indeed, in times of oxidative stress, nuclear translocation of AIF was found to occur concurrently with perturbations to the Trx-AIF interaction. Once localized in the nucleus, reduced Trx1 hindered the interaction between AIF and DNA, thereby bringing about an attenuation of AIF-mediated DNA damage. In conclusion, characterization of the Trx-AIF interaction has led to an understanding of the effect of reduced Trx1 on possibly regulating AIF-dependent cell death through impeding AIF-mediated DNA damage. Importantly, identification of the novel interaction between Trx1 and AIF has provided opportunities to design and develop therapeutically relevant strategies that either promote or prevent this protein-protein interaction for the treatment of different disease states. |
| |
| Keywords: | Apoptosis inducing factor Thioredoxin Oxidative stress Protein-protein interaction |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
