Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors

Elife. 2021 Dec 31;10:e68213. doi: 10.7554/eLife.68213.

Abstract

Human mitochondria express a genome that encodes thirteen core subunits of the oxidative phosphorylation system (OXPHOS). These proteins insert into the inner membrane co-translationally. Therefore, mitochondrial ribosomes engage with the OXA1L-insertase and membrane-associated proteins, which support membrane insertion of translation products and early assembly steps into OXPHOS complexes. To identify ribosome-associated biogenesis factors for the OXPHOS system, we purified ribosomes and associated proteins from mitochondria. We identified TMEM223 as a ribosome-associated protein involved in complex IV biogenesis. TMEM223 stimulates the translation of COX1 mRNA and is a constituent of early COX1 assembly intermediates. Moreover, we show that SMIM4 together with C12ORF73 interacts with newly synthesized cytochrome b to support initial steps of complex III biogenesis in complex with UQCC1 and UQCC2. Our analyses define the interactome of the human mitochondrial ribosome and reveal novel assembly factors for complex III and IV biogenesis that link early assembly stages to the translation machinery.

Keywords: assembly; biochemistry; cell biology; chemical biology; mitochondria; oxidative phosphorylation; ribosome; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochromes b
  • Electron Transport Complex IV / metabolism
  • Humans
  • Membrane Proteins / metabolism*
  • Mitochondrial Ribosomes / metabolism*
  • Oxidative Phosphorylation*
  • Protein Biosynthesis
  • RNA, Messenger
  • Ribosomal Proteins / genetics*

Substances

  • Membrane Proteins
  • RNA, Messenger
  • Ribosomal Proteins
  • Cytochromes b
  • Electron Transport Complex IV

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.