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

Dennerlein, S., Poerschke, S., Oeljeklaus, S., Wang, C., Richter-Dennerlein, R., Sattmann, J., et al. (2021). Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors. eLife, 10: e68213. doi:10.7554/eLife.68213.

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Dennerlein, S., Author
Poerschke, S., Author
Oeljeklaus, S., Author
Wang, C., Author
Richter-Dennerlein, R., Author
Sattmann, J., Author
Bauermeister, D., Author
Hanitsch, E., Author
Stoldt, S.1, Author           
Langer, T., Author
Jakobs, S.1, Author           
Warscheid, B., Author
Rehling, P.2, Author           
Affiliations:
1Research Group of Mitochondrial Structure and Dynamics, MPI for Biophysical Chemistry, Max Planck Society, ou_578566              
2Max Planck Fellow Peter Rehling, ou_1298545              

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 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.

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Language(s): eng - English
 Dates: 2021-12-31
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.7554/eLife.68213
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Title: eLife
Source Genre: Journal
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Pages: - Volume / Issue: 10 Sequence Number: e68213 Start / End Page: - Identifier: ISSN: 2050-084X