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Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts
Coenzyme Q (CoQ) lipids are ancient electron carriers that, in eukaryotes, function in the mitochondrial respiratory chain. In mitochondria, CoQ lipids are built by an inner membrane–associated, multicomponent, biosynthetic pathway via successive steps of isoprenyl tail polymerization, 4-hydroxybenz...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446851/ https://www.ncbi.nlm.nih.gov/pubmed/30674579 http://dx.doi.org/10.1083/jcb.201808044 |
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author | Subramanian, Kelly Jochem, Adam Le Vasseur, Maxence Lewis, Samantha Paulson, Brett R. Reddy, Thiruchelvi R. Russell, Jason D. Coon, Joshua J. Pagliarini, David J. Nunnari, Jodi |
author_facet | Subramanian, Kelly Jochem, Adam Le Vasseur, Maxence Lewis, Samantha Paulson, Brett R. Reddy, Thiruchelvi R. Russell, Jason D. Coon, Joshua J. Pagliarini, David J. Nunnari, Jodi |
author_sort | Subramanian, Kelly |
collection | PubMed |
description | Coenzyme Q (CoQ) lipids are ancient electron carriers that, in eukaryotes, function in the mitochondrial respiratory chain. In mitochondria, CoQ lipids are built by an inner membrane–associated, multicomponent, biosynthetic pathway via successive steps of isoprenyl tail polymerization, 4-hydroxybenzoate head-to-tail attachment, and head modification, resulting in the production of CoQ. In yeast, we discovered that head-modifying CoQ pathway components selectively colocalize to multiple resolvable domains in vivo, representing supramolecular assemblies. In cells engineered with conditional ON or OFF CoQ pathways, domains were strictly correlated with CoQ production and substrate flux, respectively, indicating that CoQ lipid intermediates are required for domain formation. Mitochondrial CoQ domains were also observed in human cells, underscoring their conserved functional importance. CoQ domains within cells were highly enriched adjacent to ER–mitochondria contact sites. Together, our data suggest that CoQ domains function to facilitate substrate accessibility for processive and efficient CoQ production and distribution in cells. |
format | Online Article Text |
id | pubmed-6446851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64468512019-10-01 Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts Subramanian, Kelly Jochem, Adam Le Vasseur, Maxence Lewis, Samantha Paulson, Brett R. Reddy, Thiruchelvi R. Russell, Jason D. Coon, Joshua J. Pagliarini, David J. Nunnari, Jodi J Cell Biol Research Articles Coenzyme Q (CoQ) lipids are ancient electron carriers that, in eukaryotes, function in the mitochondrial respiratory chain. In mitochondria, CoQ lipids are built by an inner membrane–associated, multicomponent, biosynthetic pathway via successive steps of isoprenyl tail polymerization, 4-hydroxybenzoate head-to-tail attachment, and head modification, resulting in the production of CoQ. In yeast, we discovered that head-modifying CoQ pathway components selectively colocalize to multiple resolvable domains in vivo, representing supramolecular assemblies. In cells engineered with conditional ON or OFF CoQ pathways, domains were strictly correlated with CoQ production and substrate flux, respectively, indicating that CoQ lipid intermediates are required for domain formation. Mitochondrial CoQ domains were also observed in human cells, underscoring their conserved functional importance. CoQ domains within cells were highly enriched adjacent to ER–mitochondria contact sites. Together, our data suggest that CoQ domains function to facilitate substrate accessibility for processive and efficient CoQ production and distribution in cells. Rockefeller University Press 2019-04-01 2019-01-23 /pmc/articles/PMC6446851/ /pubmed/30674579 http://dx.doi.org/10.1083/jcb.201808044 Text en © 2019 Subramanian et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Subramanian, Kelly Jochem, Adam Le Vasseur, Maxence Lewis, Samantha Paulson, Brett R. Reddy, Thiruchelvi R. Russell, Jason D. Coon, Joshua J. Pagliarini, David J. Nunnari, Jodi Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts |
title | Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts |
title_full | Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts |
title_fullStr | Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts |
title_full_unstemmed | Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts |
title_short | Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts |
title_sort | coenzyme q biosynthetic proteins assemble in a substrate-dependent manner into domains at er–mitochondria contacts |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446851/ https://www.ncbi.nlm.nih.gov/pubmed/30674579 http://dx.doi.org/10.1083/jcb.201808044 |
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