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

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 suppo...

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Autores principales: Dennerlein, Sven, Poerschke, Sabine, Oeljeklaus, Silke, Wang, Cong, Richter-Dennerlein, Ricarda, Sattmann, Johannes, Bauermeister, Diana, Hanitsch, Elisa, Stoldt, Stefan, Langer, Thomas, Jakobs, Stefan, Warscheid, Bettina, Rehling, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719881/
https://www.ncbi.nlm.nih.gov/pubmed/34969438
http://dx.doi.org/10.7554/eLife.68213
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author Dennerlein, Sven
Poerschke, Sabine
Oeljeklaus, Silke
Wang, Cong
Richter-Dennerlein, Ricarda
Sattmann, Johannes
Bauermeister, Diana
Hanitsch, Elisa
Stoldt, Stefan
Langer, Thomas
Jakobs, Stefan
Warscheid, Bettina
Rehling, Peter
author_facet Dennerlein, Sven
Poerschke, Sabine
Oeljeklaus, Silke
Wang, Cong
Richter-Dennerlein, Ricarda
Sattmann, Johannes
Bauermeister, Diana
Hanitsch, Elisa
Stoldt, Stefan
Langer, Thomas
Jakobs, Stefan
Warscheid, Bettina
Rehling, Peter
author_sort Dennerlein, Sven
collection PubMed
description 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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spelling pubmed-87198812022-01-05 Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors Dennerlein, Sven Poerschke, Sabine Oeljeklaus, Silke Wang, Cong Richter-Dennerlein, Ricarda Sattmann, Johannes Bauermeister, Diana Hanitsch, Elisa Stoldt, Stefan Langer, Thomas Jakobs, Stefan Warscheid, Bettina Rehling, Peter eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2021-12-31 /pmc/articles/PMC8719881/ /pubmed/34969438 http://dx.doi.org/10.7554/eLife.68213 Text en © 2021, Dennerlein et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Dennerlein, Sven
Poerschke, Sabine
Oeljeklaus, Silke
Wang, Cong
Richter-Dennerlein, Ricarda
Sattmann, Johannes
Bauermeister, Diana
Hanitsch, Elisa
Stoldt, Stefan
Langer, Thomas
Jakobs, Stefan
Warscheid, Bettina
Rehling, Peter
Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors
title Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors
title_full Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors
title_fullStr Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors
title_full_unstemmed Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors
title_short Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors
title_sort defining the interactome of the human mitochondrial ribosome identifies smim4 and tmem223 as respiratory chain assembly factors
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719881/
https://www.ncbi.nlm.nih.gov/pubmed/34969438
http://dx.doi.org/10.7554/eLife.68213
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