Yurim Ji1, Soomin Chae1, Hyun-Kyung Lee1, Inji Park1, Chowon Kim1, Tayaba Ismail1, Youni Kim1, Jeen-Woo Park1, Oh-Shin Kwon1, Beom-Sik Kang1, Dong-Seok Lee1, Jong-Sup Bae2, Sang-Hyun Kim3, Pyung-Gon Moon4, Moon-Chang Baek4, Mae-Ja Park5, In Sup Kil6, Sue Goo Rhee6, Joon Kim7, Yang Hoon Huh8, Jong-Yeon Shin9, Kyoung-Jin Min10, Taeg Kyu Kwon10, Dong Gil Jang11, Hyun Ae Woo12, Taejoon Kwon11, Tae Joo Park11, Hyun-Shik Lee1. 1. 1 KNU-Center for Nonlinear Dynamics, CMRI, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University , Daegu, South Korea . 2. 2 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University , Daegu, South Korea . 3. 3 Department of Pharmacology, College of Medicine, Kyungpook National University , Daegu, South Korea . 4. 4 Department of Molecular Medicine, College of Medicine, Kyungpook National University , Daegu, South Korea . 5. 5 Department of Anatomy, College of Medicine, Kyungpook National University , Daegu, South Korea . 6. 6 Yonsei Biomedical Research Institute, Yonsei University College of Medicine , Seoul, South Korea . 7. 7 Graduate School of Medical Science and Engineering , Taejon, South Korea . 8. 8 Electron Microscopy Center, Korea Basic Science Institute, Cheongju-si , Chungcheongbuk-do, South Korea . 9. 9 Genomic Medicine Institute, Medical Research Center, Seoul National University , Macrogen, Inc., Seoul, South Korea . 10. 10 Department of Immunology, School of Medicine, Keimyung University , Daegu, South Korea . 11. 11 School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST) , Ulsan, South Korea . 12. 12 College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University , Seoul, South Korea .
Abstract
AIMS: Peroxiredoxin5 (Prdx5), a thioredoxin peroxidase, is an antioxidant enzyme that is widely studied for its antioxidant properties and protective roles in neurological and cardiovascular disorders. This study is aimed at investigating the functional significance of Prdx5 in mitochondria and at analyzing its roles in ciliogenesis during the process of vertebrate development. RESULTS: We found that several Prdx genes were strongly expressed in multiciliated cells in developing Xenopus embryos, and their peroxidatic functions were crucial for normal cilia development. Depletion of Prdx5 increased levels of cellular reactive oxygen species (ROS), consequently leading to mitochondrial dysfunction and abnormal cilia formation. Proteomic and transcriptomic approaches revealed that excessive ROS accumulation on Prdx5 depletion subsequently reduced the expression level of pyruvate kinase (PK), a key metabolic enzyme in energy production. We further confirmed that the promotor activity of PK was significantly reduced on Prdx5 depletion and that the reduction in PK expression and its promoter activity led to ciliary defects observed in Prdx5-depleted cells. INNOVATION: Our data revealed the novel relationship between ROS and Prdx5 and the consequent effects of this interaction on vertebrate ciliogenesis. The normal process of ciliogenesis is interrupted by the Prdx5 depletion, resulting in excessive ROS levels and suggesting cilia as vulnerable targets of ROS. CONCLUSION: Prdx5 plays protective roles in mitochondria and is critical for normal cilia development by regulating the levels of ROS. The loss of Prdx5 is associated with excessive production of ROS, resulting in mitochondrial dysfunction and aberrant ciliogenesis.
AIMS: Peroxiredoxin5 (Prdx5), a thioredoxin peroxidase, is an antioxidant enzyme that is widely studied for its antioxidant properties and protective roles in neurological and cardiovascular disorders. This study is aimed at investigating the functional significance of Prdx5 in mitochondria and at analyzing its roles in ciliogenesis during the process of vertebrate development. RESULTS: We found that several Prdx genes were strongly expressed in multiciliated cells in developing Xenopus embryos, and their peroxidatic functions were crucial for normal cilia development. Depletion of Prdx5 increased levels of cellular reactive oxygen species (ROS), consequently leading to mitochondrial dysfunction and abnormal cilia formation. Proteomic and transcriptomic approaches revealed that excessive ROS accumulation on Prdx5 depletion subsequently reduced the expression level of pyruvate kinase (PK), a key metabolic enzyme in energy production. We further confirmed that the promotor activity of PK was significantly reduced on Prdx5 depletion and that the reduction in PK expression and its promoter activity led to ciliary defects observed in Prdx5-depleted cells. INNOVATION: Our data revealed the novel relationship between ROS and Prdx5 and the consequent effects of this interaction on vertebrate ciliogenesis. The normal process of ciliogenesis is interrupted by the Prdx5 depletion, resulting in excessive ROS levels and suggesting cilia as vulnerable targets of ROS. CONCLUSION:Prdx5 plays protective roles in mitochondria and is critical for normal cilia development by regulating the levels of ROS. The loss of Prdx5 is associated with excessive production of ROS, resulting in mitochondrial dysfunction and aberrant ciliogenesis.