MTERF3 regulates mitochondrial ribosome biogenesis in invertebrates and mammals.

• Main Authors: Anna Wredenberg, Marie Lagouge, Ana Bratic, Metodi D Metodiev, Henrik Spåhr, Arnaud Mourier, Christoph Freyer, Benedetta Ruzzenente, Luke Tain, Sebastian Grönke, Francesca Baggio, Christian Kukat, Elisabeth Kremmer, Rolf Wibom, Paola Loguercio Polosa, Bianca Habermann, Linda Partridge, Chan Bae Park, Nils-Göran Larsson
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2013-01-01
• Series: PLoS Genetics
• Online Access: http://europepmc.org/articles/PMC3536695?pdf=render

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.