Shabalina 2018 MiP2018

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Irina Shabalina
Elovl2-ablation leads to mitochondrial phospholipid remodeling and reduced oxidative phosphorylation capacity in mouse liver mitochondria.

Link: MiP2018

Shabalina IG, Gomez Rodriguez A, Talamonti E, Naudi A, Kalinovich A, Pauter AM, Barja G, Pamplona R, Dobrzyn P, Nedergaard J, Jacobsson A (2018)

Event: MiP2018

COST Action MitoEAGLE

ELOVL2 (elongase of omega 3 and 6 fatty acids) was found to be the most powerful single epigenetic biomarker of aging [1] and could be involved in the control of body metabolism in general [2]. Here we show that the Elovl2-ablation drastically reduced the omega-3 docosahexaenoic acid (22:6n-3) (DHA) level in the liver mitochondrial membrane, changed phospholipid composition, reducing phosphatidylserine and phosphatidylinositol but increasing cardiolipin (typical mitochondria phospholipid) and sphingomyelin (rare mitochondrial phospholipid). These changes in lipid composition were associated with low mitochondrial Respiratory Control Ratio, high sensitivity to uncoupling by fatty acids and accelerated spontaneous permeabilisation. High sensitivity to mitochondrial permeabilisation were not related to high oxidative damage of proteins: the level of the protein markers of glycoxidation (carboxyethyl lysine and carboxymethyl lysine), and the specific carbonyls (glutamic and aminoadipic semialdehydes) was not different between wild-type and Elovl2 KO mice. Notably, the lipoxidation-dependent marker of protein modification malondialdehyde lysine was significantly lower in Elovl2 KO mice as compared to wild-type. Protein content of major respiratory chain enzymes and F1Fo ATP-synthase was not changed, whereas ATP/ADP-carrier and Voltage dependent anion carrier (VDAC) were upregulated, which may explain the high sensitivity to uncoupling and permeabilisation.

In conclusion, the data imply that a high phospholipid content of DHA is essential for maintaining normal mitochondrial function.


Bioblast editor: Plangger M, Kandolf G O2k-Network Lab: SE Stockholm Nedergaard J


Labels: MiParea: mt-Membrane, Genetic knockout;overexpression  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Liver 





Affiliations

Shabalina Irina G(1), Gómez Rodríguez A(1,2), Talamonti E(1), Naudi A(3), Kalinovich A(1), Pauter AM(1), Barja G(2), Pamplona R(3), Dobrzyn P(4), Nedergaard J(1), Jacobsson A(1)

  1. Dept Molecular Biosciences, Wenner-Gren Inst, Stockholm Univ, Sweden. – irina.shabalina@su.se
  2. Dept Animal Physiology II, Fac Biological Sciences, Complutense Univ, Madrid
  3. Dept Experimental Medicine, Univ Lleida, Biomedical Research Inst Lleida; Spain
  4. Dept Biochemistry, Nencki Inst Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

References

  1. Garagnani P, Bacalini MG, Pirazzini C, Gori D, Giuliani C, Mari D, Di Blasio AM, Gentilini D, Vitale G, Collino S, Rezzi S, Castellani G, Capri M, Salvioli S, Franceschi C (2012) Methylation of ELOVL2 gene as a new epigenetic marker of age. Aging Cell 11:1132–4.
  2. Pauter AM, Olsson P, Asadi A, Herslof B, Csikasz RI, Zadravec D, Jacobsson A (2014) Elovl2 ablation demonstrates that systemic DHA is endogenously produced and is essential for lipid homeostasis in mice. J Lipid Res 55:718-28.