Journal article

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

Ayenachew Bezawork-Geleta, He Wen, LanFeng Dong, Bing Yan, Jelena Vider, Stepana Boukalova, Linda Krobova, Katerina Vanova, Renata Zobalova, Margarita Sobol, Pavel Hozak, Silvia Magalhaes Novais, Veronika Caisova, Pavel Abaffy, Ravindra Naraine, Ying Pang, Thiri Zaw, Ping Zhang, Radek Sindelka, Mikael Kubista Show all

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2018

Abstract

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 wit..

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Grants

Awarded by Czech Science Foundation


Awarded by Czech Health Foundation grant


Awarded by National Science Foundation of Korea


Awarded by Czech Science Foundation grant


Awarded by Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education Science and Technology


Awarded by Bio-Synergy Research Project through the National Research Foundation of Korea - Ministry of Education Science and Technology


Awarded by Technology Agency of the Czech Republic


Awarded by IMG grant


Awarded by Institute of Biotechnology


Awarded by BIOCEV European Regional Development Fund


Awarded by National Key Research and Development Program of China


Awarded by Science and Technology Foundation of Shenzhen City


Awarded by Ministry of Education, Youth and Sports of the Czech Republic (Czech-BioImaging)


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Funding Acknowledgements

The work was supported in part by the ARC Discovery grant, Czech Science Foundation (15 02203S) and Czech Health Foundation grant (17 30138A) to J.N., bilateral funding by the Czech Science Foundation and National Science Foundation of Korea (17-01192J/NRF-2016K2A9A1A06921853) to J.N. and S.P., Czech Science Foundation grant (17-20904S and 16-22823S) to J.R., funding by Genesis Oncology Trust, the Cancer Society of New Zealand and the Health Research Council of New Zealand to M.V.B., the Basic Science Research Program (2009-83533), the Bio-Synergy Research Project (NRF-2015M3A9C4075818) through the National Research Foundation of Korea funded by the Ministry of Education Science and Technology and Ministry of Science, ICT and Future Planning to S.P., by the Technology Agency of the Czech Republic (TE01020118) IMG grant (RVO: 68378050) to M.S. and P.H., and the institutional support of the Institute of Biotechnology RVO: 86652036, by the BIOCEV European Regional Development Fund CZ.1.05/1.100, and by the Intramural Research Program of the NIH, NICHD. H.W. was supported by the National Key Research and Development Program of China (2017YFA0503900) and Science and Technology Foundation of Shenzhen City (JCYJ20170302144650949). Proteomic analysis was facilitated by access to the Australian Proteome Analysis Facility supported in part by the Australian Government's National Collaborative Research Infrastructure Strategy. The electron microscopy data were produced at the Microscopy Centre-Electron Microscopy Core Facility (Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic) supported by Ministry of Education, Youth and Sports of the Czech Republic (LM2015062 Czech-BioImaging).