Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria

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Gómez Rodríguez, Alexia and Talamonti, Emanuela and Naudí, Alba and Kalinovich, Anastasia V. and Pauter, Anna M. and Barja de Quiroga, Gustavo and Bengtsson, Tore and Jacobsson, Anders and Pamplona, Reinald and Shabalina, Irina G. (2022) Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria. Nutrients, 14 . ISSN Electronic: 2072-6643

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Official URL: https://doi.org/10.3390/nu14030559




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, 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. 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 malondialdehyde-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 the 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. 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 electron 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


Item Type:Article
Uncontrolled Keywords:Docosahexaenoic acid (DHA) deficiency; Mitochondrial function; Polyunsaturated fatty acids; Membrane permeabilization; Oxidative damage markers; Adenine nucleotide translocase
Subjects:Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Mammals
ID Code:73639
Deposited On:18 Jul 2022 12:02
Last Modified:02 Aug 2022 11:26

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