MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome

Cell Metab. 2011 May 4;13(5):527-39. doi: 10.1016/j.cmet.2011.04.002.


Precise control of mitochondrial DNA gene expression is critical for regulation of oxidative phosphorylation capacity in mammals. The MTERF protein family plays a key role in this process, and its members have been implicated in regulation of transcription initiation and site-specific transcription termination. We now demonstrate that a member of this family, MTERF4, directly controls mitochondrial ribosomal biogenesis and translation. MTERF4 forms a stoichiometric complex with the ribosomal RNA methyltransferase NSUN4 and is necessary for recruitment of this factor to the large ribosomal subunit. Loss of MTERF4 leads to defective ribosomal assembly and a drastic reduction in translation. Our results thus show that MTERF4 is an important regulator of translation in mammalian mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Cardiomyopathies
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA, Mitochondrial / genetics
  • Gene Expression Regulation, Developmental*
  • Immunoprecipitation
  • Integrases / metabolism
  • Methyltransferases
  • Mice
  • Mice, Knockout
  • Mitochondria / genetics*
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / genetics
  • Mitochondrial Diseases / pathology
  • Mitochondrial Proteins / genetics*
  • Oxidative Phosphorylation
  • Protein Biosynthesis*
  • Protein Methyltransferases / metabolism*
  • RNA, Ribosomal / genetics
  • Ribosomal Proteins / physiology*
  • Ribosomes / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transcription Factors / genetics*
  • Transcription, Genetic


  • Carrier Proteins
  • DNA, Mitochondrial
  • MTERF4 protein, mouse
  • Mitochondrial Proteins
  • RNA, Ribosomal
  • Ribosomal Proteins
  • Transcription Factors
  • Methyltransferases
  • Protein Methyltransferases
  • SHTAP protein, mouse
  • Cre recombinase
  • Integrases