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

Authors :
Sven Dennerlein
Sabine Poerschke
Silke Oeljeklaus
Cong Wang
Ricarda Richter-Dennerlein
Johannes Sattmann
Diana Bauermeister
Elisa Hanitsch
Stefan Stoldt
Thomas Langer
Stefan Jakobs
Bettina Warscheid
Peter Rehling
Source :
eLife, Vol 10 (2021)
Publication Year :
2021
Publisher :
eLife Sciences Publications Ltd, 2021.

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.

Details

Language :
English
ISSN :
2050084X
Volume :
10
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.8625a3117ca49bd95b34fa7d3c7007d
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.68213