Any budding scientist knows that oil and water don’t mix. However, for our largely water-filled cells to thrive, nature needs to devise clever ways to make and move around the lipids—fat and oil-like compounds—that comprise membranes and other key cellular parts. One such lipid, coenzyme Q(CoQ) is an essential component of the energy-producing pathways in mitochondria.
Scientists in the Pagliarini Lab at the Morgridge Institute for Research and the lab of Matteo Dal Peraro at EPFL’s Institute of Bioengineering in Switzerland combined structural, biochemical, and computational approaches to study how COQ9—a protein vital to the production of CoQ—binds and helps shepherd immature CoQ through its biosynthesis.
“Our findings are exciting because they reveal new aspects of how a custom protein may be able find and grab a specific lipid from within a membrane and pass it along to other enzymes in the production line,” says Dave Pagliarini, Morgridge investigator and associate professor of biochemistry at the University of Wisconsin–Madison. “It’s possible that our work may inform new strategies to treat lipid deficiency disorders that are recalcitrant to current therapies, including many CoQ-related diseases.”
The results were published in the Feb. 21 issue of Molecular Cell and can also be accessed online.
“It’s now clear that COQ9 is part of a large complex of proteins that coalesces on the mitochondrial membrane when cells need to make more CoQ,” Pagliarini says. “We are excited to work out how this complicated ‘machine’ is built and operates. CoQ deficiency impacts many rare and common diseases, and understanding these basic underpinnings of its biosynthesis is a first step toward fixing problems when they arise.”
Read more about the study from the EPFL Institute of Bioengineering partners.