TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I.
TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I.
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DOI：
10.1073/pnas.2100558118
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发表时间：
2021-03-30
影响因子：
11.1
通讯作者：
Walker JE
中科院分区：
文献类型：
--
作者：
Carroll J;He J;Ding S;Fearnley IM;Walker JE
富含能量的化合物的氧化产生质子动力，质子的化学势差，穿过线粒体的内膜。质子动力驱动ATP合酶膜结构域中转子的转动。这种旋转提供能量来合成维持生命所需的ATP。人ATP合酶由27个核编码蛋白和2个线粒体编码亚基组成，在细胞器内膜中组装，形成代表F1催化结构域、外周柄和转子膜部分c8环的中间模块。C8环的组装需要两种膜相关蛋白TMEM70和TMEM242的参与。人线粒体ATP合成酶是一种结合在细胞器内膜上的具有旋转作用的分子机器。在质子动力的驱动下，转子的转动提供了能量，使ADP和磷酸盐生成ATP。在18种29种组分蛋白中，ATP 6和ATP 8为线粒体基因产物，其余为输入细胞器的核基因产物。ATP合酶是由它们通过代表酶的主要结构元件的中间模块组装而成的。一个这样的模块是c8环，其提供酶转子的膜部分，并且其组装受到另一种跨膜（TMEM）蛋白TMEM 70的影响。我们已经表明，亚基c与TMEM70和另一个迄今尚未确定的线粒体跨膜蛋白，TMEM242相互作用。TMEM242的缺失，类似于TMEM70的缺失，影响但不完全消除ATP合酶的组装，并且在较小程度上影响呼吸酶复合物I、III和IV的组装。TMEM70和TMEM242的缺失一起阻止ATP合酶的组装，并且对复合物I的影响增强。去除TMEM242，但不去除TMEM70，也影响亚基ATP 6、ATP 8、j和k引入酶中。TMEM 70和TMEM 242与线粒体复合物I组装（MCIA）复合物相互作用，该复合物支持复合物I的膜臂的组装。TMEM70和TMEM242与MCIA的相互作用可能是ATP合酶和复合物I组装或调节其水平的一部分。
The oxidation of energy rich compounds generates a proton motive force, a chemical potential difference for protons, across the inner membranes of the mitochondria. The proton motive force drives the turning of the rotor in the membrane domain of the ATP synthase. This rotation provides the energy to synthesize the ATP required to sustain life. The assembly in the inner organellar membrane of human ATP synthase from 27 nuclear encoded proteins and 2 mitochondrially encoded subunits involves the formation of intermediate modules representing the F1-catalytic domain, the peripheral stalk, and the c8-ring in the membrane part of the rotor. The assembly of the c8-ring requires the participation of two membrane-associated proteins, TMEM70 and, as we demonstrate, TMEM242. Human mitochondrial ATP synthase is a molecular machine with a rotary action bound in the inner organellar membranes. Turning of the rotor, driven by a proton motive force, provides energy to make ATP from ADP and phosphate. Among the 29 component proteins of 18 kinds, ATP6 and ATP8 are mitochondrial gene products, and the rest are nuclear gene products that are imported into the organelle. The ATP synthase is assembled from them via intermediate modules representing the main structural elements of the enzyme. One such module is the c8-ring, which provides the membrane sector of the enzyme’s rotor, and its assembly is influenced by another transmembrane (TMEM) protein, TMEM70. We have shown that subunit c interacts with TMEM70 and another hitherto unidentified mitochondrial transmembrane protein, TMEM242. Deletion of TMEM242, similar to deletion of TMEM70, affects but does not completely eliminate the assembly of ATP synthase, and to a lesser degree the assembly of respiratory enzyme complexes I, III, and IV. Deletion of TMEM70 and TMEM242 together prevents assembly of ATP synthase and the impact on complex I is enhanced. Removal of TMEM242, but not of TMEM70, also affects the introduction of subunits ATP6, ATP8, j, and k into the enzyme. TMEM70 and TMEM242 interact with the mitochondrial complex I assembly (the MCIA) complex that supports assembly of the membrane arm of complex I. The interactions of TMEM70 and TMEM242 with MCIA could be part of either the assembly of ATP synthase and complex I or the regulation of their levels.
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DOI：
10.1002/anie.202011548
发表时间：
2021-02-23
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Giachin G;Jessop M;Bouverot R;Acajjaoui S;Saïdi M;Chretien A;Bacia-Verloop M;Signor L;Mas PJ;Favier A;Borel Meneroud E;Hons M;Hart DJ;Kandiah E;Boeri Erba E;Buisson A;Leonard G;Gutsche I;Soler-Lopez M
通讯作者：
Soler-Lopez M
影响因子：
3.3
作者：
Moller-Hergt, Braulio Vargas;Carlstrom, Andreas;Ott, Martin
通讯作者：
Ott, Martin
影响因子：
29
作者：
Guerrero-Castillo, Sergio;Baertling, Fabian;Nijtmans, Leo
通讯作者：
Nijtmans, Leo
DOI：
10.1073/pnas.1722086115
发表时间：
2018-03-20
影响因子：
11.1
作者：
He, Jiuya;Ford, Holly C.;Walker, John E.
通讯作者：
Walker, John E.
影响因子：
11.4
作者：
FEARNLEY, IM;WALKER, JE
通讯作者：
WALKER, JE