title: Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance.
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.
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: YongJoong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Hag Dong
authors.initials: HD
authors.lastname: Kim
authors.affiliation: Laboratory of Biochemistry, School of Life Sciences & Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address: joonkim@korea.ac.kr.
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
mesh_terms: D003474:Curcumin / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008954:Models, Biological; D010084:Oxidation-Reduction / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D012269:Ribosomal Proteins; C402118:TOMM70 protein, human; C044152:ribosomal protein S3; C024829:8-hydroxyguanine; D006147:Guanine; D006861:Hydrogen Peroxide; D003474:Curcumin
keywords: HSP70; HSP90; Mitochondria; ROS; Ribosomal protein S3