Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria
The fatty acid elongase elongation of very long-chain fatty acids protein 2 (ELOVL2)controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3,docosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn-6)in vivo. Expectedly,Elovl2-ablation drastically reduced the DHA and DPAn-6 in liver mitochondrial membranes. Unex-pectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation.The lipid peroxidation process was not involved in PUFAs reduction since malondialdehyde-lysine(MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrialrespiratory chain proteins remained unchanged. Still, membrane remodeling was associated withthe high voltage-dependent anion channel (VDAC) and adenine nucleotide translocase 2 (ANT2),a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mi-tochondrial function was impaired despite preserved content of the respiratory chain proteins andthe absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coeffi-cients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fattyacid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume andnumber of peroxisomes increased as revealed by transmission electron microscopy. In conclusion,the results imply that endogenous DHA production is vital for the normal function of mouse livermitochondria and could be relevant not only for mice but also for human metabolism. ; This study was supported by grants from the Swedish Science Council (VR-NT 2017-04715and VR-MT 2019-01508). This research was also funded in part by the Spanish Ministry of Science,Innovation, and Universities (grant RTI2018-099200-B-I00), and the Generalitat of Catalonia: Agencyfor Management of University and Research Grants (2017SGR696) to R.P. This study was co-financedby FEDER funds from the European Union ("A way to build Europe"). IRB Lleida ...
