Human F1F0 ATP synthase, mitochondrial ultrastructure and OXPHOS impairment: a (super-)complex matter?
Human F1F0 ATP synthase, mitochondrial ultrastructure and OXPHOS impairment: a (super-)complex matter?
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DOI：
10.1371/journal.pone.0075429
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Paumard P
中科院分区：
文献类型：
--
作者：
Habersetzer J;Larrieu I;Priault M;Salin B;Rossignol R;Brèthes D;Paumard P
线粒体形态发生是细胞生理的一个重要过程。这对于这种双膜分隔的细胞器的正常功能是必不可少的，因为它确保了内膜以一种非常有序的模式排列，称为嵴。在酵母中，线粒体ATP合酶能够形成二聚体，这些二聚体可以组装成低聚物。两个亚基（e和g）参与了这种超分子组织。编码这些亚基的基因的缺失对ATP合成酶单体的组装或活性没有影响，只影响其二聚化和寡聚化。同时，ATP合成酶超复合体的亚基e和g的缺失促进了线粒体超微结构的修饰，这表明ATP合成酶寡聚化参与了嵴形态的形成。在培养的哺乳动物细胞中，shrna介导的亚基e和g的下调影响ATP合成酶的稳定性，导致可用功能酶减少50%。当亚基e和g的表达被抑制时，ATP合成酶二聚体和低聚物在原生电泳检测中含量较低。出乎意料的是，哺乳动物ATP合成酶二聚化/寡聚化损伤对呼吸链具有功能性影响，导致OXPHOS活性降低。最后，ATP合酶的这些结构和功能改变对细胞器本身产生强烈的影响，导致线粒体网络的分裂和线粒体超微结构的破坏。与酵母不同的是，ATP合成酶寡聚过程的损伤极大地影响了线粒体ATP的产生。因此，我们提出编码亚基e和g的基因突变或缺失可能具有生理病理意义。
Mitochondrial morphogenesis is a key process of cell physiology. It is essential for the proper function of this double membrane-delimited organelle, as it ensures the packing of the inner membrane in a very ordered pattern called cristae. In yeast, the mitochondrial ATP synthase is able to form dimers that can assemble into oligomers. Two subunits (e and g) are involved in this supramolecular organization. Deletion of the genes encoding these subunits has no effect on the ATP synthase monomer assembly or activity and only affects its dimerization and oligomerization. Concomitantly, the absence of subunits e and g and thus, of ATP synthase supercomplexes, promotes the modification of mitochondrial ultrastructure suggesting that ATP synthase oligomerization is involved in cristae morphogenesis. We report here that in mammalian cells in culture, the shRNA-mediated down-regulation of subunits e and g affects the stability of ATP synthase and results in a 50% decrease of the available functional enzyme. Comparable to what was shown in yeast, when subunits e and g expression are repressed, ATP synthase dimers and oligomers are less abundant when assayed by native electrophoresis. Unexpectedly, mammalian ATP synthase dimerization/oligomerization impairment has functional consequences on the respiratory chain leading to a decrease in OXPHOS activity. Finally these structural and functional alterations of the ATP synthase have a strong impact on the organelle itself leading to the fission of the mitochondrial network and the disorganization of mitochondrial ultrastructure. Unlike what was shown in yeast, the impairment of the ATP synthase oligomerization process drastically affects mitochondrial ATP production. Thus we propose that mutations or deletions of genes encoding subunits e and g may have physiopathological implications.
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影响因子：
7.8
作者：
ALLEN, RD;SCHROEDER, CC;FOK, AK
通讯作者：
FOK, AK
影响因子：
30.8
作者：
Kissler, S;Stern, P;Wicker, LS
通讯作者：
Wicker, LS
影响因子：
11.4
作者：
Paumard, P;Vaillier, J;Velours, J
通讯作者：
Velours, J
影响因子：
4.8
作者：
Bustos, DM;Velours, J
通讯作者：
Velours, J
DOI：
10.1016/j.bbamcr.2009.02.011
发表时间：
2009-05-01
影响因子：
5.1
作者：
Kucharczyk, Roza;Rak, Malgorzata;di Rago, Jean-Paul
通讯作者：
di Rago, Jean-Paul