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 drasticall...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/71806 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/71806 |
| Access Level: | acceso abierto |
| Palabra clave: | 591.1 599.32 Docosahexaenoic acid (DHA) deficiency Mitochondrial function Polyunsaturated fatty acids Membrane permeabilization Oxidative damage markers Adenine nucleotide translocase Fisiología animal (Biología) Mamíferos 2401.13 Fisiología Animal 2401.18 Mamíferos |
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Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondriaGómez Rodríguez, AlexiaTalamonti, EmanuelaNaudí, AlbaKalinovich, Anastasia V.Pauter, Anna M.Barja de Quiroga, GustavoBengtsson, ToreJacobsson, AndersPamplona, ReinaldShabalina, Irina G.591.1599.32Docosahexaenoic acid (DHA) deficiencyMitochondrial functionPolyunsaturated fatty acidsMembrane permeabilizationOxidative damage markersAdenine nucleotide translocaseFisiología animal (Biología)Mamíferos2401.13 Fisiología Animal2401.18 MamíferosThe 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 metabolismMDPIUniversidad Complutense de Madrid20222022-01-0120222022-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/71806reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/718062026-06-02T12:44:21Z |
| dc.title.none.fl_str_mv |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria |
| title |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria |
| spellingShingle |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria Gómez Rodríguez, Alexia 591.1 599.32 Docosahexaenoic acid (DHA) deficiency Mitochondrial function Polyunsaturated fatty acids Membrane permeabilization Oxidative damage markers Adenine nucleotide translocase Fisiología animal (Biología) Mamíferos 2401.13 Fisiología Animal 2401.18 Mamíferos |
| title_short |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria |
| title_full |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria |
| title_fullStr |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria |
| title_full_unstemmed |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria |
| title_sort |
Elovl2-Ablation leads to mitochondrial membrane fatty acid remodeling and reduced efficiency in mouse liver mitochondria |
| dc.creator.none.fl_str_mv |
Gómez Rodríguez, Alexia Talamonti, Emanuela Naudí, Alba Kalinovich, Anastasia V. Pauter, Anna M. Barja de Quiroga, Gustavo Bengtsson, Tore Jacobsson, Anders Pamplona, Reinald Shabalina, Irina G. |
| author |
Gómez Rodríguez, Alexia |
| author_facet |
Gómez Rodríguez, Alexia Talamonti, Emanuela Naudí, Alba Kalinovich, Anastasia V. Pauter, Anna M. Barja de Quiroga, Gustavo Bengtsson, Tore Jacobsson, Anders Pamplona, Reinald Shabalina, Irina G. |
| author_role |
author |
| author2 |
Talamonti, Emanuela Naudí, Alba Kalinovich, Anastasia V. Pauter, Anna M. Barja de Quiroga, Gustavo Bengtsson, Tore Jacobsson, Anders Pamplona, Reinald Shabalina, Irina G. |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad Complutense de Madrid |
| dc.subject.none.fl_str_mv |
591.1 599.32 Docosahexaenoic acid (DHA) deficiency Mitochondrial function Polyunsaturated fatty acids Membrane permeabilization Oxidative damage markers Adenine nucleotide translocase Fisiología animal (Biología) Mamíferos 2401.13 Fisiología Animal 2401.18 Mamíferos |
| topic |
591.1 599.32 Docosahexaenoic acid (DHA) deficiency Mitochondrial function Polyunsaturated fatty acids Membrane permeabilization Oxidative damage markers Adenine nucleotide translocase Fisiología animal (Biología) Mamíferos 2401.13 Fisiología Animal 2401.18 Mamíferos |
| description |
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 |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022-01-01 2022 2022-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.14352/71806 |
| url |
https://hdl.handle.net/20.500.14352/71806 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
MDPI |
| publisher.none.fl_str_mv |
MDPI |
| dc.source.none.fl_str_mv |
reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM) |
| instname_str |
Universidad Complutense de Madrid (UCM) |
| reponame_str |
Docta Complutense |
| collection |
Docta Complutense |
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|
| repository.mail.fl_str_mv |
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1869403953422139392 |
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15,300719 |