2. Academic Validation
  3. Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance

Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance

  • Biochim Biophys Acta. 2013 Dec;1833(12):2943-2952. doi: 10.1016/j.bbamcr.2013.07.015.
YongJoong Kim 1,  Hag Dong Kim 1,  Joon Kim 2
Affiliations

Affiliations

  • 1 Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
  • 2 Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address: joonkim@korea.ac.kr.
PMID: 23911537 DOI: 10.1016/j.bbamcr.2013.07.015
Abstract

Ribosomal protein S3 (rpS3) is known to play critical roles in ribosome biogenesis and DNA repair. When cellular ROS levels increase, the mitochondrial genes are highly vulnerable to DNA damage. Increased ROS induces rpS3 accumulation in the mitochondria for DNA repair while significantly decreasing the cellular protein synthesis. For the entrance into the mitochondria, the accumulation of rpS3 was regulated by interaction with HSP90, HSP70, and TOM70. Pretreatment with geldanamycin, which binds to the ATP pocket of HSP90, significantly decreased the interaction of rpS3 with HSP90 and stimulated the accumulation of rpS3 in the mitochondria. Furthermore, cellular ROS was decreased and mtDNA damage was rescued when levels of rpS3 were increased in the mitochondria. Therefore, we concluded that when mitochondrial DNA damages accumulate due to increased levels of ROS, rpS3 accumulates in the mitochondria to repair damaged DNA due to the decreased interaction between rpS3 and HSP90 in the cytosol.

Keywords

HSP70; HSP90; Mitochondria; ROS; Ribosomal protein S3.

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