Polyunsaturated fatty acids directly regulate coenzyme Q biosynthesis
Authors: del RIo Lucia Fernandez , Burón María Isabel , Clarke Catherine F. , Villalba José Manuel 
Published: June 2021

Biological membranes adapt their phospholipid composition according to the major lipid source present in the diet. Different dietary sources may modify the lipid pattern and produce biochemical alterations in cells, especially in mitochondrial membranes. For example, sources of polyunsaturated fatty acids, such as soybean or fish oil, will generate membranes more susceptible to oxidative stress than will sources of saturated or monounsaturated fatty acids, such as animal fat or olive oil, respectively. Previous studies revealed that different dietary fats also influenced the mitochondrial levels of coenzyme Q (Q), a lipid present in all organisms. Apart from participating as an electron and proton carrier in the mitochondrial electron transport chain, Q serves numerous cellular functions including metabolism, antioxidant protection, and the regulation of signal transduction. We used a hepatocellular model of Hepa1‐6 cells treated with different lipid emulsions, and focused on the regulation of Q biosynthesis and the ultrastructure of the mitochondria. Our results indicate that treatment with unsaturated fatty acids increased Q levels, which corresponded to an increase in Q biosynthetic rate in the case of polyunsaturated fatty acids (PUFA) but not in the case of monounsaturated fatty acids (MUFA). Moreover, our results indicate that PUFA regulate the different Q isoforms, and promote the biosynthesis of Q10 over Q9 thus decreasing Q9/Q10 ratio. Since most of the cellular Q is located in mitochondria, the structure, number, size and distribution of this organelle greatly influences the overall content of Q in cells. We studied the ultrastructure and the abundance of mitochondria in order to evaluate whether the regulation of Q levels by fatty acids involved an alteration of mitochondrial ultrastructure and/or mitochondrial abundance. Electron microscopy micrographs of cells showed that cells treated with n‐3 PUFA showed significantly increased mitochondrial volume and the number of mitochondria per cell, explaining in part the increase of Q levels previously described. However, these alterations in the mitochondrial ultrastructure do not explain the alteration of the Q9/Q10 ratio. Further experiments focused on the mevalonate pathway showed that the alteration of the Q9/Q10 ratio can be explained by PUFA‐mediated inhibition of farnesyl diphosphate synthase, a key enzyme in this pathway. However, the observed increase of Q biosynthesis may implicate additional target(s). Immunostaining analyses reveal that PUFA exert an stimulatory effect on some of the COQ proteins involved in Q biosynthesis pathway. Further studies will be needed to fully understand the exact regulation that fatty acids exert on Q metabolism and mitochondrial ultrastructure.Support or Funding InformationBFU2015‐64630‐R and BFU2011‐23578 Projects from the Spanish Ministery of Economy. 1R01AG028125‐01A1 Project from NIH. FPU12/03398 Scholarship from the Spanish Ministery of Education, Culture and Sport.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.