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

A. Bezawork-Geleta, H. Wen, L. Dong, B. Yan, J. Vider, S. Boukalova, L. Krobova, K. Vanova, R. Zobalova, M. Sobol, P. Hozak, SM. Novais, V. Caisova, P. Abaffy, R. Naraine, Y. Pang, T. Zaw, P. Zhang, R. Sindelka, M. Kubista, S. Zuryn, MP. Molloy,...

. 2018 ; 9 (1) : 2221. [pub] 20180607

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19000664

Grant support
NV17-30138A MZ0 CEP Register

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.

Australian Proteome Analysis Facility Macquarie University North Ryde 2109 NSW Australia

Clem Jones Centre for Ageing Dementia Research Queensland Brain Institute University of Queensland Brisbane 4072 Qld Australia

College of Pharmacy Natural Product Research Institute Seoul National University Seoul 08826 Korea

Department of Biochemistry and Molecular Biology Shenzhen University School of Medicine Shenzhen 518060 China College of Pharmacy Natural Product Research Institute Seoul National University Seoul 08826 Korea

Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD USA

Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda 20892 MD USA Faculty of Science University of South Bohemia Ceske Budejovice 37005 Czech Republic

Institute of Biotechnology Czech Academy of Sciences Prague West 25250 Czech Republic

Institute of Biotechnology Czech Academy of Sciences Prague West 25250 Czech Republic TATAA Biocenter Gothenburg 41103 Sweden

Institute of Molecular Genetics Czech Academy of Sciences Prague 14220 Czech Republic

Malaghan Institute of Medical Research Wellington 6242 New Zealand

School of Medical Sciences Griffith University Southport 4222 Qld Australia

School of Medical Sciences Griffith University Southport 4222 Qld Australia Clem Jones Centre for Ageing Dementia Research Queensland Brain Institute University of Queensland Brisbane 4072 Qld Australia

School of Medical Sciences Griffith University Southport 4222 Qld Australia Institute of Biotechnology Czech Academy of Sciences Prague West 25250 Czech Republic

References provided by Crossref.org

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