The human mitochondrial ribosome recycling factor is essential for cell viability.
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.
Rorbach
Joanna
J
Mitochondrial Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Richter
Ricarda
R
Wessels
Hans J
HJ
Wydro
Mateusz
M
Pekalski
Marcin
M
Farhoud
Murtada
M
Kühl
Inge
I
Gaisne
Mauricette
M
Bonnefoy
Nathalie
N
Smeitink
Jan A
JA
Lightowlers
Robert N
RN
Chrzanowska-Lightowlers
Zofia M A
ZM
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
D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D012269:Ribosomal Proteins; D029702:Schizosaccharomyces pombe Proteins; C087267:ribosome releasing factor
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