Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex.
Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex.
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DOI：
10.1371/journal.ppat.1009301
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发表时间：
2021-03
期刊：
影响因子：
6.7
通讯作者：
Sheiner L
中科院分区：
文献类型：
--
作者：
Maclean AE;Bridges HR;Silva MF;Ding S;Ovciarikova J;Hirst J;Sheiner L
线粒体电子传递链（mETC）和F1Fo-ATP合成酶对真核细胞的能量和代谢至关重要。顶复合体是引起弓形虫病和疟疾等人类疾病的重要病原体，在其复杂生命周期的每个已知阶段都依赖于它们的mETC。在这里，我们使用络合物分析蛋白质组学方法，对弓形虫的mETC复合物和F1Fo-ATP合成酶进行了表征。在弓形虫的II、IV和F1Fo-ATP合成酶复合体中鉴定并分配了60个蛋白，其中16个蛋白以前未被鉴定。值得注意的是，我们的复合物谱阐明了弓形虫复合物III的组成，这是临床上使用的药物如阿托伐醌的靶标。我们发现了两个新的同源亚基和两个新的寄生虫特异性亚基，其中一个在粘虫动物中广泛保守。我们证明了这四种蛋白质对复合物III的稳定性和寄生虫的生长都是必不可少的，并且表明它们的消耗会导致线粒体潜能的降低，从而支持它们作为复合物III亚基的分配。我们的研究强调了mETC和F1Fo-ATP合成酶复合物的不同亚基组成，并为未来的结构和药物发现研究奠定了基础。顶端复合体寄生虫，如弓形虫和疟原虫，会引起具有全球重要性的疾病，如弓形虫病和疟疾。线粒体电子传递链（mETC）和F1Fo-ATP合成酶为寄生虫提供能量和重要代谢物，对寄生虫的功能至关重要。在这里，使用一种称为复杂组分析的蛋白质组学技术，我们报告了弓形虫mETC和F1Fo-ATP合成酶的组成。特别是，我们首次揭示了配合物II和III的组成。配合物III是一个重要的药物靶点，但其完整的蛋白质组成尚不清楚。我们发现了新的寄生虫特异性复合体III亚基，并证明它们对寄生虫的生存和mETC的正常功能至关重要。我们的研究强调了顶端复合体mETC和F1Fo-ATP合酶的不同性质。
The mitochondrial electron transport chain (mETC) and F1Fo-ATP synthase are of central importance for energy and metabolism in eukaryotic cells. The Apicomplexa, important pathogens of humans causing diseases such as toxoplasmosis and malaria, depend on their mETC in every known stage of their complicated life cycles. Here, using a complexome profiling proteomic approach, we have characterised the Toxoplasma mETC complexes and F1Fo-ATP synthase. We identified and assigned 60 proteins to complexes II, IV and F1Fo-ATP synthase of Toxoplasma, of which 16 have not been identified previously. Notably, our complexome profile elucidates the composition of the Toxoplasma complex III, the target of clinically used drugs such as atovaquone. We identified two new homologous subunits and two new parasite-specific subunits, one of which is broadly conserved in myzozoans. We demonstrate all four proteins are essential for complex III stability and parasite growth, and show their depletion leads to decreased mitochondrial potential, supporting their assignment as complex III subunits. Our study highlights the divergent subunit composition of the apicomplexan mETC and F1Fo-ATP synthase complexes and sets the stage for future structural and drug discovery studies. Apicomplexan parasites, such as Toxoplasma and Plasmodium, cause diseases of global importance, such as toxoplasmosis and malaria. The mitochondrial electron transport chain (mETC) and F1Fo-ATP synthase, which provide the parasite with energy and important metabolites, are essential for parasite function. Here, using a proteomic technique called complexome profiling, we report the composition of the Toxoplasma mETC and F1Fo-ATP synthase. In particular, we reveal the compositions of complexes II and III for the first time. Complex III is an important drug target, yet its full protein composition was unknown. We identify new parasite-specific complex III subunits and demonstrate that they are essential for parasite survival and for proper functioning of the mETC. Our study highlights the divergent nature of the apicomplexan mETC and F1Fo-ATP synthase.
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影响因子：
9.8
作者：
Alston, Charlotte L.;Veling, Mike T.;Taylor, Robert W.
通讯作者：
Taylor, Robert W.
影响因子：
5.8
作者：
Giese, Heiko;Ackermann, Joerg;Koch, Ina
通讯作者：
Koch, Ina
影响因子：
29
作者：
Guerrero-Castillo, Sergio;Baertling, Fabian;Nijtmans, Leo
通讯作者：
Nijtmans, Leo
DOI：
10.1073/pnas.1208069109
发表时间：
2012-09-25
影响因子：
11.1
作者：
Doggett, J. Stone;Nilsen, Aaron;Riscoe, Michael K.
通讯作者：
Riscoe, Michael K.
影响因子：
2.4
作者：
FRY, M;BEESLEY, JE
通讯作者：
BEESLEY, JE