Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination.
Assembly of The Mitochondrial Complex I Assembly Complex Suggests a Regulatory Role for Deflavination.
复制标题
DOI：
10.1002/anie.202011548
复制
发表时间：
2021-02-23
期刊：
影响因子：
--
通讯作者：
Soler-Lopez M
中科院分区：
文献类型：
--
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
脂肪酸β-氧化（FAO）和氧化磷酸化（OXPHOS）是产生ATP的线粒体氧化还原过程。呼吸复合物I（负责启动OXPHOS的1 MDa多蛋白复合物）的生物发生由包括线粒体复合物I组装（MCIA）复合物的组装因子介导。 然而，MCIA综合体的组织和作用仍不清楚。在这里，我们表明，ECSIT的功能作为桥接节点的MCIA核心复杂。此外，冷冻电子显微镜以及生物化学和生物物理实验表明，ECSIT的C末端结构域直接结合FAO酶ACAD 9的残留脱氢酶结构域，并诱导其脱黄素化，将ACAD 9从其在FAO中的作用转变为MCIA因子。这些发现提供了MCIA复合物结构的结构基础，并提出了一种独特的分子机制，用于协调FAO和OXPHOS途径的调节，以确保有效的能量生产。脂肪酸氧化（FAO）和氧化磷酸化（OXPHOS）是细胞能量学的关键线粒体途径。然而，它们之间的串扰并不清楚。我们表明，线粒体复合物I组装（MCIA）复杂，所需的复合物I的生物合成，从而激活OXPHOS的分子结构，意味着一个变构脱黄素机制，关闭粮农组织。
Fatty acid β‐oxidation (FAO) and oxidative phosphorylation (OXPHOS) are mitochondrial redox processes that generate ATP. The biogenesis of the respiratory Complex I, a 1 MDa multiprotein complex that is responsible for initiating OXPHOS, is mediated by assembly factors including the mitochondrial complex I assembly (MCIA) complex. However, the organisation and the role of the MCIA complex are still unclear. Here we show that ECSIT functions as the bridging node of the MCIA core complex. Furthermore, cryo‐electron microscopy together with biochemical and biophysical experiments reveal that the C‐terminal domain of ECSIT directly binds to the vestigial dehydrogenase domain of the FAO enzyme ACAD9 and induces its deflavination, switching ACAD9 from its role in FAO to an MCIA factor. These findings provide the structural basis for the MCIA complex architecture and suggest a unique molecular mechanism for coordinating the regulation of the FAO and OXPHOS pathways to ensure an efficient energy production. Fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) are key mitochondrial pathways for cellular energetics. However, the crosstalk between them is unclear. We show that the molecular architecture of the mitochondrial Complex I assembly (MCIA) complex, required for Complex I biogenesis and thereby for activation of OXPHOS, implies an allosteric deflavination mechanism that shuts down FAO.
登录
查看更多内容
影响因子：
64.8
作者：
Fiedorczuk, Karol;Letts, James A.;Degliesposti, Gianluca;Kaszuba, Karol;Skehel, Mark;Sazanov, Leonid A.
通讯作者：
Sazanov, Leonid A.
影响因子：
56.9
作者：
Kampjut, Domen;Sazanov, Leonid A.
通讯作者：
Sazanov, Leonid A.
影响因子：
29
作者：
Guerrero-Castillo, Sergio;Baertling, Fabian;Nijtmans, Leo
通讯作者：
Nijtmans, Leo
DOI：
10.1007/978-1-4614-3573-0_4
发表时间：
2012-01-01
期刊：
MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION: NUCLEAR-ENCODED GENES, ENZYME REGULATION, AND PATHOPHYSIOLOGY
影响因子：
--
作者：
Ghezzi, Daniele;Zeviani, Massimo
通讯作者：
Zeviani, Massimo
影响因子：
16
作者：
Floyd BJ;Wilkerson EM;Veling MT;Minogue CE;Xia C;Beebe ET;Wrobel RL;Cho H;Kremer LS;Alston CL;Gromek KA;Dolan BK;Ulbrich A;Stefely JA;Bohl SL;Werner KM;Jochem A;Westphall MS;Rensvold JW;Taylor RW;Prokisch H;Kim JP;Coon JJ;Pagliarini DJ
通讯作者：
Pagliarini DJ