title: The human mitochondrial ribosome recycling factor is essential for cell viability.
abstract: The molecular mechanism of human mitochondrial translation has yet to be fully described. We are particularly interested in understanding the process of translational termination and ribosome recycling in the mitochondrion. Several candidates have been implicated, for which subcellular localization and characterization have not been reported. Here, we show that the putative mitochondrial recycling factor, mtRRF, is indeed a mitochondrial protein. Expression of human mtRRF in fission yeast devoid of endogenous mitochondrial recycling factor suppresses the respiratory phenotype. Further, human mtRRF is able to associate with Escherichia coli ribosomes in vitro and can associate with mitoribosomes in vivo. Depletion of mtRRF in human cell lines is lethal, initially causing profound mitochondrial dysmorphism, aggregation of mitoribosomes, elevated mitochondrial superoxide production and eventual loss of OXPHOS complexes. Finally, mtRRF was shown to co-immunoprecipitate a large number of mitoribosomal proteins attached to other mitochondrial proteins, including putative members of the mitochondrial nucleoid.
authors.affiliation: Mitochondrial Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Rorbach
authors.forename: Ricarda
authors.initials: R
authors.lastname: Richter
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Wessels
authors.forename: Mateusz
authors.initials: M
authors.lastname: Wydro
authors.forename: Marcin
authors.initials: M
authors.lastname: Pekalski
authors.forename: Murtada
authors.initials: M
authors.lastname: Farhoud
authors.forename: Inge
authors.initials: I
authors.lastname: Kühl
authors.forename: Mauricette
authors.initials: M
authors.lastname: Gaisne
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonnefoy
authors.forename: Jan A
authors.initials: JA
authors.lastname: Smeitink
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.forename: Zofia M A
authors.initials: ZM
authors.lastname: Chrzanowska-Lightowlers
mesh_terms: D000595:Amino Acid Sequence; D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation; D019069:Cell Respiration; D002470:Cell Survival; D004926:Escherichia coli / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000235:genetics* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D012269:Ribosomal Proteins; D029702:Schizosaccharomyces pombe Proteins; C087267:ribosome releasing factor
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