Kinetics and Mechanism of Mammalian Mitochondrial Ribosome Assembly

Publication date: 13 February 2018 Source:Cell Reports, Volume 22, Issue 7 Author(s): Daniel F. Bogenhagen, Anne G. Ostermeyer-Fay, John D. Haley, Miguel Garcia-Diaz Mammalian mtDNA encodes only 13 proteins, all essential components of respiratory complexes, synthesized by mitochondrial ribosomes. Mitoribosomes contain greatly truncated RNAs transcribed from mtDNA, including a structural tRNA in place of 5S RNA as a scaffold for binding 82 nucleus-encoded proteins, mitoribosomal proteins (MRPs). Cryoelectron microscopy (cryo-EM) studies have determined the structure of the mitoribosome, but its mechanism of assembly is unknown. Our SILAC pulse-labeling experiments determine the rates of mitochondrial import of MRPs and their assembly into intact mitoribosomes, providing a basis for distinguishing MRPs that bind at early and late stages in mitoribosome assembly to generate a working model for mitoribosome assembly. Mitoribosome assembly is a slow process initiated at the mtDNA nucleoid driven by excess synthesis of individual MRPs. MRPs that are tightly associated in the structure frequently join the complex in a coordinated manner. Clinically significant MRP mutations reported to date affect proteins that bind early on during assembly. Graphical abstract Teaser Recent cryo-EM studies provided detailed structures of the protein-rich mammalian mitoribosome, but the process of their assembly is poorly understood. Bogenhagen et al. use SILAC pulse labeling to determine the...
Source: Cell Reports - Category: Cytology Source Type: research