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53BP1 contributes to regulation of autophagic clearance of mitochondria
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 f...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366885/ https://www.ncbi.nlm.nih.gov/pubmed/28345606 http://dx.doi.org/10.1038/srep45290 |
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author | Youn, Cha Kyung Kim, Hong Beum Wu, Ting Ting Park, Sanggon Cho, Sung Il Lee, Jung-Hee |
author_facet | Youn, Cha Kyung Kim, Hong Beum Wu, Ting Ting Park, Sanggon Cho, Sung Il Lee, Jung-Hee |
author_sort | Youn, Cha Kyung |
collection | PubMed |
description | 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 (ΔΨm) 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. |
format | Online Article Text |
id | pubmed-5366885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53668852017-03-28 53BP1 contributes to regulation of autophagic clearance of mitochondria Youn, Cha Kyung Kim, Hong Beum Wu, Ting Ting Park, Sanggon Cho, Sung Il Lee, Jung-Hee Sci Rep Article 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 (ΔΨm) 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. Nature Publishing Group 2017-03-27 /pmc/articles/PMC5366885/ /pubmed/28345606 http://dx.doi.org/10.1038/srep45290 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Youn, Cha Kyung Kim, Hong Beum Wu, Ting Ting Park, Sanggon Cho, Sung Il Lee, Jung-Hee 53BP1 contributes to regulation of autophagic clearance of mitochondria |
title | 53BP1 contributes to regulation of autophagic clearance of mitochondria |
title_full | 53BP1 contributes to regulation of autophagic clearance of mitochondria |
title_fullStr | 53BP1 contributes to regulation of autophagic clearance of mitochondria |
title_full_unstemmed | 53BP1 contributes to regulation of autophagic clearance of mitochondria |
title_short | 53BP1 contributes to regulation of autophagic clearance of mitochondria |
title_sort | 53bp1 contributes to regulation of autophagic clearance of mitochondria |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366885/ https://www.ncbi.nlm.nih.gov/pubmed/28345606 http://dx.doi.org/10.1038/srep45290 |
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