title: 53BP1 contributes to regulation of autophagic clearance of mitochondria.
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 (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.
authors.affiliation: Laboratory of Genomic Instability and Cancer therapeutics, Cancer Mutation Research Center, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.|Department of premedical Sciences, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.
authors.forename: Cha Kyung
authors.initials: CK
authors.lastname: Youn
authors.affiliation: Laboratory of Genomic Instability and Cancer therapeutics, Cancer Mutation Research Center, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.|Department of premedical Sciences, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.
authors.forename: Hong Beum
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Laboratory of Genomic Instability and Cancer therapeutics, Cancer Mutation Research Center, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.|Department of Cellular and Molecular Medicine, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, Hemato-oncology, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.
authors.forename: Sanggon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Laboratory of Genomic Instability and Cancer therapeutics, Cancer Mutation Research Center, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.|Department of Cellular and Molecular Medicine, Chosun University School of Medicine, 375 Seosuk-dong, Gwangju 61452, Republic of Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D063306:Mitophagy / Q000502:physiology; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; D044767:Ubiquitin-Protein Ligases