title: Identification of interacting partners of Human Mpv17-like protein with a mitigating effect of mitochondrial dysfunction through mtDNA damage.
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.
authors.affiliation: Division of Life Science, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Organization for Life Science Advancement Programs, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. Electronic address: riida@u-fukui.ac.jp.
authors.forename: Reiko
authors.initials: R
authors.lastname: Iida
authors.affiliation: Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Ueki
authors.affiliation: Organization for Life Science Advancement Programs, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan; Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yasuda
mesh_terms: D000968:Antimycin A / Q000008:administration & dosage; D002460:Cell Line; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000235:genetics / Q000378:metabolism; D000074002:DNA Polymerase gamma; D004260:DNA Repair / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins
chemical_list: C091247:BCAP31 protein, human; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; C511128:MPV17L protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C526722:RPS14 protein, human; C578290:RPS3 protein, human; D012269:Ribosomal Proteins; C499631:TFAM protein, human; D014157:Transcription Factors; D029867:Xenopus Proteins; D000968:Antimycin A; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human
keywords: Mitochondrial DNA; Mitochondrial dysfunction; Mpv17 family; Oxidative stress