Peroxiredoxin 3 deficiency induces cardiac hypertrophy and dysfunction by impaired mitochondrial quality control.

Autor:	Sonn SK; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea. Electronic address: ssk999@ewha.ac.kr., Song EJ; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea; Department of Veterinary Physiology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea., Seo S; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Kim YY; Peripheral Neuropathy Research Center, Department of Translational Biomedical Sciences, College of Medicine, Dong-A University, Busan 49201, Republic of Korea., Um JH; Peripheral Neuropathy Research Center, Department of Translational Biomedical Sciences, College of Medicine, Dong-A University, Busan 49201, Republic of Korea., Yeo FJ; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Lee DS; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Jeon S; Department of Biological Sciences and Biotechnology, Major in Bio-Vaccine Engineering, Andong National University, Andong 36729, Korea., Lee MN; Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea., Jin J; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Kweon HY; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Kim TK; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Kim S; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Moon SH; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Rhee SG; College of Medicine Severance Biomedical Science, Yonsei University Seoul, 03722, Republic of Korea., Chung J; SRC Center for Systems Geroscience, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, 1 Gwanak-Ro, Gwanak-Gu, Seoul 08826, Republic of Korea., Yang J; Department of Radiology, Yonsei University Seoul, 120-752, Republic of Korea., Han J; Department of Physiology & Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Busan, Republic of Korea., Choi EY; Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, 06273, Republic of Korea., Lee SB; Department of Brain Sciences, DGIST, Daegu, 42988, Republic of Korea., Yun J; Peripheral Neuropathy Research Center, Department of Translational Biomedical Sciences, College of Medicine, Dong-A University, Busan 49201, Republic of Korea., Oh GT; Heart-Immune-Brain Network Research Center, Department of Life Science, Ewha Womans University, Seoul, 03760, Republic of Korea. Electronic address: gootaeg@ewha.ac.kr.
Jazyk:	angličtina
Zdroj:	Redox biology [Redox Biol] 2022 May; Vol. 51, pp. 102275. Date of Electronic Publication: 2022 Feb 28.
DOI:	10.1016/j.redox.2022.102275
Abstrakt:	Mitochondrial quality control (MQC) consists of multiple processes: the prevention of mitochondrial oxidative damage, the elimination of damaged mitochondria via mitophagy and mitochondrial fusion and fission. Several studies proved that MQC impairment causes a plethora of pathological conditions including cardiovascular diseases. However, the precise molecular mechanism by which MQC reverses mitochondrial dysfunction, especially in the heart, is unclear. The mitochondria-specific peroxidase Peroxiredoxin 3 (Prdx3) plays a protective role against mitochondrial dysfunction by removing mitochondrial reactive oxygen species. Therefore, we investigated whether Prdx3-deficiency directly leads to heart failure via mitochondrial dysfunction. Fifty-two-week-old Prdx3-deficient mice exhibited cardiac hypertrophy and dysfunction with giant and damaged mitochondria. Mitophagy was markedly suppressed in the hearts of Prdx3-deficient mice compared to the findings in wild-type and Pink1-deficient mice despite the increased mitochondrial damage induced by Prdx3 deficiency. Under conditions inducing mitophagy, we identified that the damaged mitochondrial accumulation of PINK1 was completely inhibited by the ablation of Prdx3. We propose that Prdx3 interacts with the N-terminus of PINK1, thereby protecting PINK1 from proteolytic cleavage in damaged mitochondria undergoing mitophagy. Our results provide evidence of a direct association between MQC dysfunction and cardiac function. The dual function of Prdx3 in mitophagy regulation and mitochondrial oxidative stress elimination further clarifies the mechanism of MQC in vivo and thereby provides new insights into developing a therapeutic strategy for mitochondria-related cardiovascular diseases such as heart failure. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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