Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints

被引：52

作者：

Bezawork-Geleta, Ayenachew ^{[1
,2
]}

Wen, He ^{[3
,4
]}

Dong, LanFeng ^{[1
]}

Yan, Bing ^{[1
]}

Vider, Jelena ^{[1
]}

Boukalova, Stepana ^{[5
]}

Krobova, Linda ^{[5
]}

Vanova, Katerina ^{[5
]}

Zobalova, Renata ^{[5
]}

Sobol, Margarita ^{[6
]}

Hozak, Pavel ^{[6
]}

Novais, Silvia Magalhaes ^{[5
]}

Caisova, Veronika ^{[7
,8
]}

Abaffy, Pavel ^{[5
]}

Naraine, Ravindra ^{[5
]}

Pang, Ying ^{[7
]}

Zaw, Thiri ^{[9
]}

Zhang, Ping ^{[1
]}

Sindelka, Radek ^{[5
]}

Kubista, Mikael ^{[5
,10
]}

Zuryn, Steven ^{[2
]}

Molloy, Mark P. ^{[9
]}

Berridge, Michael V. ^{[11
]}

Pacak, Karel ^{[7
]}

Rohlena, Jakub ^{[5
]}

Park, Sunghyouk ^{[4
]}

Neuzil, Jiri ^{[1
,5
]}

机构：

[1] Griffith Univ, Sch Med Sci, Southport, Qld 4222, Australia

[2] Univ Queensland, Queensland Brain Inst, Clem Jones Ctr Ageing Dementia Res, Brisbane, Qld 4072, Australia

[3] Shenzhen Univ, Sch Med, Dept Biochem & Mol Biol, Shenzhen 518060, Peoples R China

[4] Seoul Natl Univ, Nat Prod Res Inst, Coll Pharm, Seoul 08826, South Korea

[5] Czech Acad Sci, Inst Biotechnol, Prague 25250, Czech Republic

[6] Czech Acad Sci, Inst Mol Genet, Prague 14220, Czech Republic

[7] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA

[8] Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic

[9] Macquarie Univ, Australian Proteome Anal Facil, N Ryde, NSW 2109, Australia

[10] TATAA Bioctr, S-41103 Gothenburg, Sweden

[11] Malaghan Inst Med Res, Wellington 6242, New Zealand

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

新加坡国家研究基金会; 美国国家科学基金会;

关键词：

PYRUVATE-KINASE M2; MITOCHONDRIAL-DNA MUTATIONS; SUCCINATE-DEHYDROGENASE; PYRIMIDINE SYNTHESIS; CELL-METABOLISM; PROTEIN-LEVELS; BREAST-CANCER; TCA CYCLE; RNA; PHEOCHROMOCYTOMA;

D O I：

10.1038/s41467-018-04603-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

共 86 条

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