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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
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.
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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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