Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.
Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.
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DOI：
10.1371/journal.pone.0034402
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stanley WC
中科院分区：
文献类型：
--
作者：
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
线粒体可以通过线粒体通透性过渡孔（MPTP）的打开而去极化并引发细胞死亡。我们最近发现，线粒体膜中长链n3多不饱和脂肪酸（PUFA）二十二碳六烯酸（DHA; 22:6n3）的增加和n6 PUFA花生四烯酸（ARA; 20:4n6）的消耗与诱导MPTP开放所需的更大的Ca2+负荷有关。本研究通过在大鼠饮食中添加DHA、ARA或DHA+ARA组合来控制线粒体磷脂组成，持续10周。对分离线粒体的心脏功能或呼吸没有影响。线粒体磷脂分析显示，补充DHA增加了线粒体膜上的DHA并置换了ARA，而补充ARA或DHA+ARA增加了ARA并耗尽了亚油酸（18:2 . 6）。磷脂分析显示了类似的模式，特别是在心磷脂中。补充ARA或DHA+ARA可减少80%的四脂油基心磷脂，亚油酸侧链被ARA取代。DHA和ARA组均延迟Ca2+诱导的MPTP开放，但DHA+ARA组与对照饮食相似。综上所述，膳食DHA或ARA引起的线粒体膜磷脂脂肪酸组成的改变与诱导MPTP开放所需的更大的累积Ca2+负荷有关。此外，如果被超长链n3或n6 PUFAs取代，高水平的四丙油酰心磷脂对正常线粒体功能不是必需的。
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 Ca2+ 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 Ca2+-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 Ca2+ 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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影响因子：
10.8
作者：
Duda, Monika K.;O'Shea, Karen M.;Stanley, William C.
通讯作者：
Stanley, William C.
DOI：
10.1016/0378-4347(93)80441-6
发表时间：
1993-09-08
期刊：
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS
影响因子：
--
作者：
INGALLS, ST;KRIARIS, MS;HOPPEL, CL
通讯作者：
HOPPEL, CL
影响因子：
4.3
作者：
Khairallah, Ramzi J.;Sparagna, Genevieve C.;Stanley, William C.
通讯作者：
Stanley, William C.
影响因子：
4.2
作者：
Farina, Emily K.;Kiel, Douglas P.;Tucker, Katherine L.
通讯作者：
Tucker, Katherine L.
影响因子：
3.9
作者：
Halestrap, Andrew P.
通讯作者：
Halestrap, Andrew P.