BIOMAT Database Logo BIOMAT Database Logo

XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage. 2015

Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
Key Laboratory of Genomics and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.

Xeroderma pigmentosum group D (XPD/ERCC2) encodes an ATP-dependent helicase that plays essential roles in both transcription and nucleotide excision repair of nuclear DNA, however, whether or not XPD exerts similar functions in mitochondria remains elusive. In this study, we provide the first evidence that XPD is localized in the inner membrane of mitochondria, and cells under oxidative stress showed an enhanced recruitment of XPD into mitochondrial compartment. Furthermore, mitochondrial reactive oxygen species production and levels of oxidative stress-induced mitochondrial DNA (mtDNA) common deletion were significantly elevated, whereas capacity for oxidative damage repair of mtDNA was markedly reduced in both XPD-suppressed human osteosarcoma (U2OS) cells and XPD-deficient human fibroblasts. Immunoprecipitation-mass spectrometry analysis was used to identify interacting factor(s) with XPD and TUFM, a mitochondrial Tu translation elongation factor was detected to be physically interacted with XPD. Similar to the findings in XPD-deficient cells, mitochondrial common deletion and oxidative damage repair capacity in U2OS cells were found to be significantly altered after TUFM knock-down. Our findings clearly demonstrate that XPD plays crucial role(s) in protecting mitochondrial genome stability by facilitating an efficient repair of oxidative DNA damage in mitochondria.

UI MeSH Term Description Entries
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D010444 Peptide Elongation Factor Tu A protein found in bacteria and eukaryotic mitochondria which delivers aminoacyl-tRNA's to the A site of the ribosome. The aminoacyl-tRNA is first bound to a complex of elongation factor Tu containing a molecule of bound GTP. The resulting complex is then bound to the 70S initiation complex. Simultaneously the GTP is hydrolyzed and a Tu-GDP complex is released from the 70S ribosome. The Tu-GTP complex is regenerated from the Tu-GDP complex by the Ts elongation factor and GTP. Elongation Factor Tu,EF-Tu,Eucaryotic Elongation Factor Tu,Protein Synthesis Elongation Factor Tu,eEF-Tu,EF Tu,Factor Tu, Elongation,eEF Tu
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D017384 Sequence Deletion Deletion of sequences of nucleic acids from the genetic material of an individual. Deletion Mutation,Deletion Mutations,Deletion, Sequence,Deletions, Sequence,Mutation, Deletion,Mutations, Deletion,Sequence Deletions
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D051759 Xeroderma Pigmentosum Group D Protein A DNA helicase that is a component of TRANSCRIPTION FACTOR TFIIH. It plays an essential role in NUCLEOTIDE EXCISION REPAIR, and mutations in this protein are associated with XERODERMA PIGMENTOSUM. ERCC2 Protein,Excision Repair Cross-Complementing Rodent Repair Deficiency, Group 2 Protein,Xeroderma Pigmentosum Complementation Group D Protein,Excision Repair Cross Complementing Rodent Repair Deficiency, Group 2 Protein
D054629 Genome, Mitochondrial The genetic complement of MITOCHONDRIA as represented in their DNA. Mitochondrial Genome,Genomes, Mitochondrial,Mitochondrial Genomes

Related Publications

Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
MMS19 localizes to mitochondria and protects the mitochondrial genome from oxidative damage.
February 2018, Biochemistry and cell biology = Biochimie et biologie cellulaire,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
The human MSH5 (MutSHomolog 5) protein localizes to mitochondria and protects the mitochondrial genome from oxidative damage.
November 2012, Mitochondrion,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome.
January 2015, PloS one,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
Metallothionein protects DNA from oxidative damage.
April 1993, The Biochemical journal,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity.
June 2012, Aging cell,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
Glutathione S-transferase pi localizes in mitochondria and protects against oxidative stress.
May 2009, Free radical biology & medicine,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
The Sub1 nuclear protein protects DNA from oxidative damage.
January 2016, Molecular and cellular biochemistry,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons.
December 2004, Acta pharmacologica Sinica,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
Mitochondria, oxidative DNA damage, and aging.
October 2000, Journal of the American Aging Association,
Jing Liu, and Hongbo Fang, and Zhenfen Chi, and Zan Wu, and Di Wei, and Dongliang Mo, and Kaifeng Niu, and Adayabalam S Balajee, and Tom K Hei, and Linghu Nie, and Yongliang Zhao
Mitochondrial genome undergoes de novo DNA methylation that protects mtDNA against oxidative damage during the peri-implantation window.
July 2022, Proceedings of the National Academy of Sciences of the United States of America,
Copied contents to your clipboard!