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

Yong Joong Kim; Hag Dong Kim; Joon Kim

doi:10.1016/j.bbamcr.2013.07.015

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

Yong Joong Kim
, Hag Dong Kim
, Joon Kim^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

73 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2943-2952
Number of pages	10
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1833
Issue number	12
DOIs	https://doi.org/10.1016/j.bbamcr.2013.07.015
Publication status	Published - 2013 Dec

Bibliographical note

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.

Keywords

HSP70
HSP90
Mitochondria
ROS
Ribosomal protein S3

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.bbamcr.2013.07.015

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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.",

keywords = "HSP70, HSP90, Mitochondria, ROS, Ribosomal protein S3",

author = "Kim, \{Yong Joong\} and Kim, \{Hag Dong\} and Joon Kim",

note = "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. ",

year = "2013",

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doi = "10.1016/j.bbamcr.2013.07.015",

language = "English",

volume = "1833",

pages = "2943--2952",

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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

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DO - 10.1016/j.bbamcr.2013.07.015

M3 - Article

C2 - 23911537

AN - SCOPUS:84883010357

SN - 0167-4889

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JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

IS - 12

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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