Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health.
Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health.
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DOI：
10.1242/jcs.258399
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发表时间：
2021-07-01
影响因子：
4
通讯作者：
Collinson I
中科院分区：
文献类型：
--
作者：
Knapp-Wilson A;Pereira GC;Buzzard E;Ford HC;Richardson A;Corey RA;Neal C;Verkade P;Halestrap AP;Gold VAM;Kuwabara PE;Collinson I
线粒体超复合物围绕单体复合物I和二聚体复合物III的保守核心形成;其中前者的亚基NDUFA 11显著地位于界面处。我们鉴定nduf-11（B0491.5）为编码NDUFA 11的秀丽隐杆线虫同源物。对于nduf-11的CRISPR-Cas9产生的敲除等位基因纯合的动物在第二幼虫（L2）发育阶段停滞。使用RNAi减少（但不消除）表达允许发育至成年，从而能够表征结果：复合物I及其超复合物的不稳定和呼吸功能的干扰。NADH脱氢酶活性的损失通过增强的复合物II活性来补偿，具有产生有害活性氧（ROS）的潜力。冷冻电子断层扫描突出了嵴的异常形态和嵴连接处和膜间隙的加宽。NDUF-11对平衡呼吸、线粒体形态和发育的需求可能是由于其参与复合体I和超复合体的维持而产生的。这突出了呼吸复合体完整性对健康的重要性以及其扰动导致线粒体疾病的可能性。总结：通过去除组装因子NDUF-11使复合物I及其超复合物失稳严重影响平衡呼吸、线粒体形态，并最终影响整个动物生理学。
Mitochondrial supercomplexes form around a conserved core of monomeric complex I and dimeric complex III; wherein a subunit of the former, NDUFA11, is conspicuously situated at the interface. We identified nduf-11 (B0491.5) as encoding the Caenorhabditis elegans homologue of NDUFA11. Animals homozygous for a CRISPR-Cas9-generated knockout allele of nduf-11 arrested at the second larval (L2) development stage. Reducing (but not eliminating) expression using RNAi allowed development to adulthood, enabling characterisation of the consequences: destabilisation of complex I and its supercomplexes and perturbation of respiratory function. The loss of NADH dehydrogenase activity was compensated by enhanced complex II activity, with the potential for detrimental reactive oxygen species (ROS) production. Cryo-electron tomography highlighted aberrant morphology of cristae and widening of both cristae junctions and the intermembrane space. The requirement of NDUF-11 for balanced respiration, mitochondrial morphology and development presumably arises due to its involvement in complex I and supercomplex maintenance. This highlights the importance of respiratory complex integrity for health and the potential for its perturbation to cause mitochondrial disease. Summary: Destabilisation of complex I and its supercomplexes by removal of the assembly factor NDUF-11 severely affects balanced respiration, mitochondrial morphology and, ultimately, whole animal physiology.
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影响因子：
29
作者：
Guerrero-Castillo, Sergio;Baertling, Fabian;Nijtmans, Leo
通讯作者：
Nijtmans, Leo
影响因子：
14.9
作者：
Drozdetskiy A;Cole C;Procter J;Barton GJ
通讯作者：
Barton GJ
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
6.3
作者：
BERENDSEN, HJC;VANDERSPOEL, D;VANDRUNEN, R
通讯作者：
VANDRUNEN, R
DOI：
10.1073/pnas.1319247110
发表时间：
2013-11-19
影响因子：
11.1
作者：
Andrews, Byron;Carroll, Joe;Walker, John E.
通讯作者：
Walker, John E.