title: MTERF3 regulates mitochondrial ribosome biogenesis in invertebrates and mammals.
abstract: Regulation of mitochondrial DNA (mtDNA) expression is critical for the control of oxidative phosphorylation in response to physiological demand, and this regulation is often impaired in disease and aging. We have previously shown that mitochondrial transcription termination factor 3 (MTERF3) is a key regulator that represses mtDNA transcription in the mouse, but its molecular mode of action has remained elusive. Based on the hypothesis that key regulatory mechanisms for mtDNA expression are conserved in metazoans, we analyzed Mterf3 knockout and knockdown flies. We demonstrate here that decreased expression of MTERF3 not only leads to activation of mtDNA transcription, but also impairs assembly of the large mitochondrial ribosomal subunit. This novel function of MTERF3 in mitochondrial ribosomal biogenesis is conserved in the mouse, thus we identify a novel and unexpected role for MTERF3 in coordinating the crosstalk between transcription and translation for the regulation of mammalian mtDNA gene expression.
authors.affiliation: Max-Planck Institute for Biology of Ageing, Köln, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Wredenberg
authors.forename: Marie
authors.initials: M
authors.lastname: Lagouge
authors.forename: Ana
authors.initials: A
authors.lastname: Bratic
authors.forename: Metodi D
authors.initials: MD
authors.lastname: Metodiev
authors.forename: Henrik
authors.initials: H
authors.lastname: Spåhr
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mourier
authors.forename: Christoph
authors.initials: C
authors.lastname: Freyer
authors.forename: Benedetta
authors.initials: B
authors.lastname: Ruzzenente
authors.forename: Luke
authors.initials: L
authors.lastname: Tain
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grönke
authors.forename: Francesca
authors.initials: F
authors.lastname: Baggio
authors.forename: Christian
authors.initials: C
authors.lastname: Kukat
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Rolf
authors.initials: R
authors.lastname: Wibom
authors.forename: Paola Loguercio
authors.initials: PL
authors.lastname: Polosa
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
authors.forename: Chan Bae
authors.initials: CB
authors.lastname: Park
authors.forename: Nils-Göran
authors.initials: NG
authors.lastname: Larsson
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D007448:Invertebrates / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics; D010085:Oxidative Phosphorylation; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004272:DNA, Mitochondrial; D029721:Drosophila Proteins; C515228:MTERF3 protein, Drosophila; D024101:Mitochondrial Proteins