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

Authors
 Seong Keun Sonn  ;  Eun Ju Song  ;  Seungwoon Seo  ;  Young Yeon Kim  ;  Jee-Hyun Um  ;  Franklin Joonyeop Yeo  ;  Da Seul Lee  ;  Sejin Jeon  ;  Mi-Ni Lee  ;  Jing Jin  ;  Hyae Yon Kweon  ;  Tae Kyeong Kim  ;  Sinai Kim  ;  Shin Hye Moon  ;  Sue Goo Rhee  ;  Jongkyeong Chung  ;  Jaemoon Yang  ;  Jin Han  ;  Eui-Young Choi  ;  Sung Bae Lee  ;  Jeanho Yun  ;  Goo Taeg Oh 
Citation
 REDOX BIOLOGY, Vol.51 : 102275, 2022-05 
Journal Title
REDOX BIOLOGY
Issue Date
2022-05
MeSH
Animals ; Cardiomegaly / genetics ; Cardiovascular Diseases* ; Heart Failure* ; Mice ; Mitochondria / genetics ; Peroxiredoxin III / genetics ; Protein Kinases
Keywords
Damaged mitochondria ; Heart failure ; Mitochondrial quality control ; Mitophagy ; PINK1 ; Peroxiredoxin 3
Abstract
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.
Files in This Item:
T202205200.pdf Download
DOI
10.1016/j.redox.2022.102275
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Yang, Jae Moon(양재문) ORCID logo https://orcid.org/0000-0001-7365-0395
Rhee, Sue Goo(이서구)
Choi, Eui Young(최의영) ORCID logo https://orcid.org/0000-0003-3732-0190
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191400
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