title: Mitochondrial ribosome assembly in health and disease.
abstract: The ribosome is a structurally and functionally conserved macromolecular machine universally responsible for catalyzing protein synthesis. Within eukaryotic cells, mitochondria contain their own ribosomes (mitoribosomes), which synthesize a handful of proteins, all essential for the biogenesis of the oxidative phosphorylation system. High-resolution cryo-EM structures of the yeast, porcine and human mitoribosomal subunits and of the entire human mitoribosome have uncovered a wealth of new information to illustrate their evolutionary divergence from their bacterial ancestors and their adaptation to synthesis of highly hydrophobic membrane proteins. With such structural data becoming available, one of the most important remaining questions is that of the mitoribosome assembly pathway and factors involved. The regulation of mitoribosome biogenesis is paramount to mitochondrial respiration, and thus to cell viability, growth and differentiation. Moreover, mutations affecting the rRNA and protein components produce severe human mitochondrial disorders. Despite its biological and biomedical significance, knowledge on mitoribosome biogenesis and its deviations from the much-studied bacterial ribosome assembly processes is scarce, especially the order of rRNA processing and assembly events and the regulatory factors required to achieve fully functional particles. This article focuses on summarizing the current available information on mitoribosome assembly pathway, factors that form the mitoribosome assembly machinery, and the effect of defective mitoribosome assembly on human health.
authors.affiliation: a Department of Biochemistry and Molecular Biology ; University of Miami Miller School of Medicine ; Miami , FL USA.
authors.forename: Dasmanthie
authors.initials: D
authors.lastname: De Silva
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Tu
authors.forename: Alexey
authors.initials: A
authors.lastname: Amunts
authors.forename: Flavia
authors.initials: F
authors.lastname: Fontanesi
authors.forename: Antoni
authors.initials: A
authors.lastname: Barrientos
mesh_terms: D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000473:pathology*; D000069396:Mitochondrial Ribosomes / Q000737:chemistry / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D020365:RNA Helicases / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012335:RNA, Ribosomal; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D020558:GTP Phosphohydrolases; D020365:RNA Helicases
keywords: mitochondrial disease; mitochondrial ribosome; mitochondrial translation; mitochondriolus; mitoribosome assembly; mitoribosome assembly factor; mitoribosome biogenesis