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Item details URL: http://open-repository.kisti.re.kr/cube/handle/open_repository/473446.do

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

author: Youn, Cha Kyung; Kim, Hong Beum; Wu, Ting Ting; Park, Sanggon; Il Cho, Sung; Lee, Jung-Hee

uri: http://open-repository.kisti.re.kr/cube/handle/open_repository/473446.do

53BP1 contributes to regulation of autophagic clearance of mitochondria