Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints.
Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints.
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DOI：
10.1038/s41467-018-04603-z
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发表时间：
2018-06-07
影响因子：
16.6
通讯作者：
Neuzil J
中科院分区：
文献类型：
--
作者：
Bezawork-Geleta A;Wen H;Dong L;Yan B;Vider J;Boukalova S;Krobova L;Vanova K;Zobalova R;Sobol M;Hozak P;Novais SM;Caisova V;Abaffy P;Naraine R;Pang Y;Zaw T;Zhang P;Sindelka R;Kubista M;Zuryn S;Molloy MP;Berridge MV;Pacak K;Rohlena J;Park S;Neuzil J
细胞的生长和存活取决于能量产生和代谢物合成之间的微妙平衡。在这里，我们提供的证据表明，一个替代的线粒体复合物II（CII）的组装，指定为CIIlow，作为一个检查点的代谢物生物合成下的生物能量的压力，细胞抑制其能量利用通过调节DNA合成和细胞周期的进展。CIIlow的消耗导致能量利用和代谢物合成的不平衡，如从头嘧啶途径的恢复和从S期解锁细胞周期停滞所证明的。通过分析来自具有散发性、SDHA和SDHB突变的患者的副神经节瘤组织，进一步证实了体外实验。这些发现表明，CIIlow是线粒体内的核心复合物，其根据能量的可用性提供细胞代谢的稳态控制。线粒体复合物II通常由四个亚基组成。在这里，作者表明，生物能量应激条件引起复合物II的部分组装变体，其将合成代谢途径转移到能量需求较少的过程。
Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy. Mitochondrial complex II is normally composed of four subunits. Here the authors show that bioenergetic stress conditions give rise to a partially assembled variant of complex II, which shifts the anabolic pathways to less energy demanding processes.
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影响因子：
4.4
作者：
Bauernfeind AL;Babbitt CC
通讯作者：
Babbitt CC
影响因子：
19
作者：
Ackerman, Daniel;Simon, M. Celeste
通讯作者：
Simon, M. Celeste
影响因子：
50.3
作者：
Fishbein L;Leshchiner I;Walter V;Danilova L;Robertson AG;Johnson AR;Lichtenberg TM;Murray BA;Ghayee HK;Else T;Ling S;Jefferys SR;de Cubas AA;Wenz B;Korpershoek E;Amelio AL;Makowski L;Rathmell WK;Gimenez-Roqueplo AP;Giordano TJ;Asa SL;Tischler AS;Cancer Genome Atlas Research Network;Pacak K;Nathanson KL;Wilkerson MD
通讯作者：
Wilkerson MD
影响因子：
4.5
作者：
Ghazalpour A;Bennett B;Petyuk VA;Orozco L;Hagopian R;Mungrue IN;Farber CR;Sinsheimer J;Kang HM;Furlotte N;Park CC;Wen PZ;Brewer H;Weitz K;Camp DG 2nd;Pan C;Yordanova R;Neuhaus I;Tilford C;Siemers N;Gargalovic P;Eskin E;Kirchgessner T;Smith DJ;Smith RD;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
7.7
作者：
Dong, Lan-Feng;Kovarova, Jaromira;Neuzil, Jiri
通讯作者：
Neuzil, Jiri