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

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Gómez Rodríguez, AlexiaStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Complutense University, Spain (author)

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

Article/chapterEnglish2022

Publisher, publication year, extent ...

2022-01-27
MDPI AG,2022
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LIBRIS-ID:oai:DiVA.org:su-202398
https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-202398URI
https://doi.org/10.3390/nu14030559DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap hsv//swe
MEDICAL AND HEALTH SCIENCES Health Sciences hsv//eng
docosahexaenoic acid (DHA) deficiency
mitochondrial function
polyunsaturated fatty acids
membrane permeabilization
oxidative damage markers
adenine nucleotide translocase

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Talamonti, EmanuelaStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)etala (author)
Naudi, Alba (author)
Kalinovich, Anastasia V.Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)akali (author)
Pauter, Anna M.Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut (author)
Barja, Gustavo (author)
Bengtsson, ToreStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)tbeng (author)
Jacobsson, AndersStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)anjac (author)
Pamplona, Reinald (author)
Shabalina, Irina G.Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)chaba (author)
Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)

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In:Nutrients: MDPI AG14:32072-6643

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