Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Elovl2-Ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria

Alexia Gómez Rodríguez
,
Emanuela Talamonti
ORCID logo ,
Alba Naudi
,
Anastasia V. Kalinovich
,
Anna M. Pauter
,
Gustavo Barja
ORCID logo ,
Tore Bengtsson
,
Anders Jacobsson
,
Reinald Pamplona
ORCID logo ,
Irina G. Shabalina
* ORCID logo
Version 1 : Received: 15 December 2021 / Approved: 16 December 2021 / Online: 16 December 2021 (10:57:36 CET)

A peer-reviewed article of this Preprint also exists.

Gómez Rodríguez, A.; Talamonti, E.; Naudi, A.; Kalinovich, A.V.; Pauter, A.M.; Barja, G.; Bengtsson, T.; Jacobsson, A.; Pamplona, R.; Shabalina, I.G. Elovl2-ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria. Nutrients 2022, 14, 559. Gómez Rodríguez, A.; Talamonti, E.; Naudi, A.; Kalinovich, A.V.; Pauter, A.M.; Barja, G.; Bengtsson, T.; Jacobsson, A.; Pamplona, R.; Shabalina, I.G. Elovl2-ablation Leads to Mitochondrial Membrane Fatty Acid Remodeling and Reduced Efficiency in Mouse Liver Mitochondria. Nutrients 2022, 14, 559.

Abstract

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, do-cosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn6) in-vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondial-dehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with high voltage-dependent anion channel (VDAC) and adenine nucleotide trans-locase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission elec-tron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.

Keywords

docosahexaenoic acid (DHA) deficiency; mitochondrial function; polyunsaturated fatty acids; membrane permeabilization; oxidative damage markers; adenine nucleotide translocase

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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