The human mitochondrial ribosome recycling factor is essential for cell viability

Nucleic Acids Res. 2008 Oct;36(18):5787-99. doi: 10.1093/nar/gkn576. Epub 2008 Sep 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Death
  • Cell Line
  • Cell Proliferation
  • Cell Respiration
  • Cell Survival
  • Escherichia coli / genetics
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Mitochondria / genetics*
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / physiology*
  • Molecular Sequence Data
  • Protein Biosynthesis
  • Reactive Oxygen Species / metabolism
  • Ribosomal Proteins / antagonists & inhibitors
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / physiology*
  • Ribosomes / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics

Substances

  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Ribosomal Proteins
  • Schizosaccharomyces pombe Proteins
  • ribosome releasing factor