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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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Cardiac mitochondrial phospholipid species composition.Values are expressed as percentage of total measured. Data are mean±SEM. CTRL, n = 14. DHA, n = 13. ARA, n = 13. DHA+ARA, n = 14. *p<0.05 vs CTRL. #p<0.05 vs DHA. †p<0.05 vs ARA.
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pone-0034402-g003: Cardiac mitochondrial phospholipid species composition.Values are expressed as percentage of total measured. Data are mean±SEM. CTRL, n = 14. DHA, n = 13. ARA, n = 13. DHA+ARA, n = 14. *p<0.05 vs CTRL. #p<0.05 vs DHA. †p<0.05 vs ARA.

Mentions: There was clear interaction between dietary DHA and ARA in their effect on phospholipid fatty acid composition, with DHA alone depleting ARA from CL, PE and PC (Figures 2 and 3, Table S1). Conversely, dietary ARA depleted DHA from PE and PC. Interestingly, the combination of DHA and ARA restored both DHA and ARA in PE and PC. Further, it gave a profile that was largely similar to the diet with ARA alone. This is illustrated in the mass spectrum (Figure 2 for CL, and Figures S1,S2,S3,S4,S5 for other phospholipids), which shows that treatment with ARA and DHA+ARA resulted in a profound shift in the profile, with an increase in peak intensities for higher molecular weight species. On the other hand, DHA had far less of an effect on the profile. As noted above, treatment with ARA or DHA+ARA, but not DHA alone, depleted linoleic acid content from total phospholipids by ∼50% (Figure 1), and the analysis of individual phospholipid species revealed that this occurred in CL, MLCL, PE PG and PC (Figure 3, Table S1).


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)

Cardiac mitochondrial phospholipid species composition.Values are expressed as percentage of total measured. Data are mean±SEM. CTRL, n = 14. DHA, n = 13. ARA, n = 13. DHA+ARA, n = 14. *p<0.05 vs CTRL. #p<0.05 vs DHA. †p<0.05 vs ARA.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0034402-g003: Cardiac mitochondrial phospholipid species composition.Values are expressed as percentage of total measured. Data are mean±SEM. CTRL, n = 14. DHA, n = 13. ARA, n = 13. DHA+ARA, n = 14. *p<0.05 vs CTRL. #p<0.05 vs DHA. †p<0.05 vs ARA.
Mentions: There was clear interaction between dietary DHA and ARA in their effect on phospholipid fatty acid composition, with DHA alone depleting ARA from CL, PE and PC (Figures 2 and 3, Table S1). Conversely, dietary ARA depleted DHA from PE and PC. Interestingly, the combination of DHA and ARA restored both DHA and ARA in PE and PC. Further, it gave a profile that was largely similar to the diet with ARA alone. This is illustrated in the mass spectrum (Figure 2 for CL, and Figures S1,S2,S3,S4,S5 for other phospholipids), which shows that treatment with ARA and DHA+ARA resulted in a profound shift in the profile, with an increase in peak intensities for higher molecular weight species. On the other hand, DHA had far less of an effect on the profile. As noted above, treatment with ARA or DHA+ARA, but not DHA alone, depleted linoleic acid content from total phospholipids by ∼50% (Figure 1), and the analysis of individual phospholipid species revealed that this occurred in CL, MLCL, PE PG and PC (Figure 3, Table S1).

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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