53BP1 contributes to regulation of autophagic clearance of mitochondria

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473446.do
DOI
10.1038/srep45290
Title
53BP1 contributes to regulation of autophagic clearance of mitochondria
Description
This work is supported by the National Research Foundation of Korea(NRF), funded by the Ministry of Science, ICT, and Future Planning[NRF-2015R1A5A2009070]. We are grateful to prof. Ho Jin You for hiscomments on the manuscript. We thank the members of the Cancer MutationResearch Center, Chosun University for technical assistance and helpfulcomments on the manuscript.
abstract
Autophagy, the primary recycling pathway within cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the cellular response to stress. Here we provide evidence that 53BP1, a DNA damage response protein, is involved in regulating mitochondrial clearance from the cell via a type of autophagy termed mitophagy. We found that when either human or mouse cells were 53BP1-deficient, there was an increase in mitochondrial abnormalities, as observed through staining intensity, aggregation, and increased mass. Moreover, a 53BP1-depleted cell population included an increased number of cells with a high mitochondrial membrane potential (Delta psi m) relative to controls, suggesting that the loss of 53BP1 prevents initiation of mitophagy thereby leading to the accumulation of damaged mitochondria. Indeed, both 53BP1 and the mitophagy-associated protein LC3 translocated to mitochondria in response to damage induced by the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). The recruitment of parkin, an E3-ubiquitin ligase, to mitochondria in response to CCCP treatment was significantly decreased in 53BP1-deficient cells. And lastly, using p53-deficient H1299 cells, we confirmed that the role of 53BP1 in mitophagy is independent of p53. These data support a model in which 53BP1 plays an important role in modulating mitochondrial homeostasis and in the clearance of damaged mitochondria.
provenance
Made available in Cube on 2018-09-28T10:19:47Z (GMT). No. of bitstreams: 0
language
English
author
Youn, Cha Kyung
Kim, Hong Beum
Wu, Ting Ting
Park, Sanggon
Il Cho, Sung
Lee, Jung-Hee
accessioned
2018-09-28T10:19:47Z
available
2018-09-28T10:19:47Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473446.do
Funder
과학기술정보통신부
Funding Program
집단연구지원
Project ID
1711048486
Jurisdiction
Rep.of Korea
Project Name
Cancer Mutation Reserch Center
rights
openAccess
type
article


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