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

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 LeeJeanho Yun, Goo Taeg Oh

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number102275
JournalRedox Biology
Volume51
DOIs
StatePublished - May 2022

Keywords

  • Damaged mitochondria
  • Heart failure
  • Mitochondrial quality control
  • Mitophagy
  • PINK1
  • Peroxiredoxin 3

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