RRC ID 37580
Author Iida R, Ueki M, Yasuda T.
Title Identification of interacting partners of Human Mpv17-like protein with a mitigating effect of mitochondrial dysfunction through mtDNA damage.
Journal Free Radic. Biol. Med.
Abstract Human Mpv17-like protein (M-LPH) has been suggested to participate in mitochondrial function. In this study, we investigated the proteins that interact with M-LPH, and identified four: H2A histone family, member X (H2AX), ribosomal protein S14 (RPS14), ribosomal protein S3 (RPS3) and B-cell receptor-associated protein 31 (Bap31). Immunofluorescence and subcellular fractionation studies revealed that M-LPH is localized predominantly in the nucleus, to some extent in a subset of mitochondria, and marginally in the cytosol. Mitochondrial M-LPH appeared as punctate foci, and these were co-localized with a subset of mitochondrial transcription factor A (TFAM) and mtDNA, indicating that M-LPH is localized in or in close proximity to mitochondrial nucleoids. RNAi-mediated knockdown of M-LPH resulted in an increase of mtDNA damage and reduced the expression of mtDNA-encoded genes. A ROS inducer, antimycin A, caused an increase in both the number and size of the mitochondrial M-LPH foci, and these foci were co-localized with two enzymes, DNA polymerase γ (POLG) and DNA ligase III (LIG3), both involved in mtDNA repair. Furthermore, knockdown of M-LPH hampered mitochondrial localization of these enzymes. Taken together, these observations suggest that M-LPH is involved in the maintenance of mtDNA and protects cells from mitochondrial dysfunction.
Volume 87
Pages 336-45
Published 2015-10
DOI 10.1016/j.freeradbiomed.2015.07.008
PII S0891-5849(15)00329-9
PMID 26165189
MeSH Antimycin A / administration & dosage Cell Line DNA Ligase ATP DNA Ligases / genetics DNA Ligases / metabolism DNA Polymerase gamma DNA Repair / genetics* DNA, Mitochondrial / genetics DNA, Mitochondrial / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism DNA-Directed DNA Polymerase / genetics DNA-Directed DNA Polymerase / metabolism Gene Expression Regulation / drug effects Histones / genetics Histones / metabolism Humans Membrane Proteins / genetics Membrane Proteins / metabolism* Mitochondria / genetics* Mitochondria / metabolism Mitochondria / pathology Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Poly-ADP-Ribose Binding Proteins Protein Binding Ribosomal Proteins / genetics Ribosomal Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism Xenopus Proteins
IF 5.657
Times Cited 0
Human and Animal Cells MDA-MB-453(RCB1192)