TY - JOUR
T1 - Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER-mitochondria contacts
AU - Subramanian, Kelly
AU - Jochem, Adam
AU - Vasseur, Maxence Le
AU - Lewis, Samantha
AU - Paulson, Brett R.
AU - Reddy, Thiruchelvi R.
AU - Russell, Jason D.
AU - Coon, Joshua J.
AU - Pagliarini, David J.
AU - Nunnari, Jodi
N1 - Publisher Copyright:
© 2019 Subramanian et al.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064199903&partnerID=8YFLogxK
U2 - 10.1083/jcb.201808044v
DO - 10.1083/jcb.201808044v
M3 - Article
C2 - 30674579
AN - SCOPUS:85064199903
SN - 0021-9525
VL - 218
SP - 1352
EP - 1368
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -