TY - JOUR
T1 - Cytoplasmic ribosomal protein S3 (rpS3) plays a pivotal role in mitochondrial DNA damage surveillance
AU - Kim, Yong Joong
AU - Kim, Hag Dong
AU - Kim, Joon
N1 - Funding Information:
We would like to thank Nikolaus Pfanner for providing Tom20cd and Tom70cd recombinant plasmid DNA. This work was supported in part by NRF - 2012R1A2A1A 01009027 grant and Korea University grant. Kim HD was supported by Korea University Fellowship.
PY - 2013/12
Y1 - 2013/12
N2 - 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.
AB - 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.
KW - HSP70
KW - HSP90
KW - Mitochondria
KW - ROS
KW - Ribosomal protein S3
UR - http://www.scopus.com/inward/record.url?scp=84883010357&partnerID=8YFLogxK
U2 - 10.1016/j.bbamcr.2013.07.015
DO - 10.1016/j.bbamcr.2013.07.015
M3 - Article
C2 - 23911537
AN - SCOPUS:84883010357
VL - 1833
SP - 2943
EP - 2952
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
IS - 12
ER -