MMS19 localizes to mitochondria and protects the mitochondrial genome from oxidative damage. 2018

Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
a Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.

MMS19 localizes to the cytoplasmic and nuclear compartments involved in transcription and nucleotide excision repair (NER). However, whether MMS19 localizes to mitochondria, where it plays a role in maintaining mitochondrial genome stability, remains unknown. In this study, we provide the first evidence that MMS19 is localized in the inner membrane of mitochondria and participates in mtDNA oxidative damage repair. MMS19 knockdown led to mitochondrial dysfunctions including decreased mtDNA copy number, diminished mtDNA repair capacity, and elevated levels of mtDNA common deletion after oxidative stress. Immunoprecipitation - mass spectrometry analysis identified that MMS19 interacts with ANT2, a protein associated with mitochondrial ATP metabolism. ANT2 knockdown also resulted in a decreased mtDNA repair capacity after oxidative damage. Our findings suggest that MMS19 plays an essential role in maintaining mitochondrial genome stability.

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
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004272 DNA, Mitochondrial Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins. Mitochondrial DNA,mtDNA
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014157 Transcription Factors Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. Transcription Factor,Factor, Transcription,Factors, Transcription
D050884 HSP72 Heat-Shock Proteins Stress-inducible members of the heat-shock proteins 70 family. HSP72 heat shock proteins function with other MOLECULAR CHAPERONES to mediate PROTEIN FOLDING and to stabilize pre-existent proteins against aggregation. Heat Shock Proteins 72,HSP-72 Protein,HSP70-1 Heat Shock Proteins,Heat Shock Protein 72,Heat-Shock Protein p72,Hsp72 Protein,HSP 72 Protein,HSP70 1 Heat Shock Proteins,HSP72 Heat Shock Proteins,Heat Shock Protein p72,Heat-Shock Proteins, HSP72,p72, Heat-Shock Protein
D054629 Genome, Mitochondrial The genetic complement of MITOCHONDRIA as represented in their DNA. Mitochondrial Genome,Genomes, Mitochondrial,Mitochondrial Genomes
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative
D034741 RNA, Small Interfering Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions. RNA, Scan,Repeat-Associated siRNA,Scan RNA,Small Scan RNA,Trans-Acting siRNA,siRNA,siRNA, Repeat-Associated,siRNA, Trans-Acting,Short Hairpin RNA,Short Interfering RNA,Small Hairpin RNA,Small Interfering RNA,scnRNA,shRNA,tasiRNA,Hairpin RNA, Short,Hairpin RNA, Small,Interfering RNA, Short,Interfering RNA, Small,RNA, Short Hairpin,RNA, Short Interfering,RNA, Small Hairpin,RNA, Small Scan,Repeat Associated siRNA,Scan RNA, Small,Trans Acting siRNA,siRNA, Repeat Associated,siRNA, Trans Acting

Related Publications

Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
June 2015, Nucleic acids research,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
November 2012, Mitochondrion,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
January 2015, PloS one,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
May 2009, Free radical biology & medicine,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
May 2011, Proceedings of the National Academy of Sciences of the United States of America,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
December 2004, Acta pharmacologica Sinica,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
August 2023, Nature communications,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
June 2012, Aging cell,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
May 2007, Biochemical and biophysical research communications,
Rui Wu, and Qunsong Tan, and Kaifeng Niu, and Yuqi Zhu, and Di Wei, and Yongliang Zhao, and Hongbo Fang
October 2005, Shock (Augusta, Ga.),
Copied contents to your clipboard!