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Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

Khairallah RJ, Kim J, O'Shea KM, O'Connell KA, Brown BH, Galvao T, Daneault C, Des Rosiers C, Polster BM, Hoppel CL, Stanley WC - PLoS ONE (2012)

Bottom Line: We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca(2+) load required to induce MPTP opening.There were no effects on cardiac function, or respiration of isolated mitochondria.In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+) load required to induced MPTP opening.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, Maryland, United States of America.

ABSTRACT
Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca(2+) load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+)-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+) load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

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Effect of phospholipase A2 inhibition on the Ca2+ retention capacity.Data are mean ±SEM. CTRL, n = 9. DHA, n = 9. ARA, n = 9. DHA+ARA, n = 10. CTRL vehicle vs CTRL inhibitors p<0.006. DHA+ARA vehicle vs DHA+ARA inhibitors p<0.01.
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pone-0034402-g005: Effect of phospholipase A2 inhibition on the Ca2+ retention capacity.Data are mean ±SEM. CTRL, n = 9. DHA, n = 9. ARA, n = 9. DHA+ARA, n = 10. CTRL vehicle vs CTRL inhibitors p<0.006. DHA+ARA vehicle vs DHA+ARA inhibitors p<0.01.

Mentions: To assess the possible role of Ca2+-dependent and –independent phospholipase A2 in Ca2+ induced MPTP opening, we assessed the effects of addition of aristolochic acid and bromoenolactone, inhibitors of phospholipase A2, on the relationship between cumulated Ca2+ load and extramitochondrial [Ca2+]. This shifted the relationship to the right in mitochondrial from the CTRL and DHA+ARA groups, but not in the DHA or ARA groups (Figure 5).


Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

Khairallah RJ, Kim J, O'Shea KM, O'Connell KA, Brown BH, Galvao T, Daneault C, Des Rosiers C, Polster BM, Hoppel CL, Stanley WC - PLoS ONE (2012)

Effect of phospholipase A2 inhibition on the Ca2+ retention capacity.Data are mean ±SEM. CTRL, n = 9. DHA, n = 9. ARA, n = 9. DHA+ARA, n = 10. CTRL vehicle vs CTRL inhibitors p<0.006. DHA+ARA vehicle vs DHA+ARA inhibitors p<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3316678&req=5

pone-0034402-g005: Effect of phospholipase A2 inhibition on the Ca2+ retention capacity.Data are mean ±SEM. CTRL, n = 9. DHA, n = 9. ARA, n = 9. DHA+ARA, n = 10. CTRL vehicle vs CTRL inhibitors p<0.006. DHA+ARA vehicle vs DHA+ARA inhibitors p<0.01.
Mentions: To assess the possible role of Ca2+-dependent and –independent phospholipase A2 in Ca2+ induced MPTP opening, we assessed the effects of addition of aristolochic acid and bromoenolactone, inhibitors of phospholipase A2, on the relationship between cumulated Ca2+ load and extramitochondrial [Ca2+]. This shifted the relationship to the right in mitochondrial from the CTRL and DHA+ARA groups, but not in the DHA or ARA groups (Figure 5).

Bottom Line: We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca(2+) load required to induce MPTP opening.There were no effects on cardiac function, or respiration of isolated mitochondria.In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+) load required to induced MPTP opening.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, University of Maryland, Baltimore, Maryland, United States of America.

ABSTRACT
Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca(2+) load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+)-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+) load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

Show MeSH
Related in: MedlinePlus