title: Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.
abstract: Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.
authors.affiliation: MRC-Mitochondrial Biology Unit, Wellcome Trust-MRC Building, Hills Road Cambridge, CB2 0XY, UK.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.forename: H M
authors.initials: HM
authors.lastname: Cooper
authors.forename: A
authors.initials: A
authors.lastname: Reyes
authors.forename: M
authors.initials: M
authors.lastname: Di Re
authors.forename: H
authors.initials: H
authors.lastname: Sembongi
authors.forename: T R
authors.initials: TR
authors.lastname: Litwin
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: K C
authors.initials: KC
authors.lastname: Neuman
authors.forename: I M
authors.initials: IM
authors.lastname: Fearnley
authors.forename: A
authors.initials: A
authors.lastname: Spinazzola
authors.forename: J E
authors.initials: JE
authors.lastname: Walker
authors.forename: I J
authors.initials: IJ
authors.lastname: Holt
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D009698:Nucleoproteins / Q000502:physiology*; D000091402:Prohibitins; D014176:Protein Biosynthesis; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D000077278:RNA, Mitochondrial; D012097:Repressor Proteins / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism
chemical_list: C549686:ATAD3A protein, human; C519737:ATAD3B protein, human; D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; C476586:GADD45GIP1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D009698:Nucleoproteins; D000091402:Prohibitins; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D012097:Repressor Proteins; D012313:RNA; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities