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, Steven Zuryn, Mark P. Molloy, Michael V. Berridge, Karel Pacak, Jakub Rohlena (), Sunghyouk Park () and Jiri Neuzil ()
Additional contact information
Ayenachew Bezawork-Geleta: Griffith University
He Wen: Shenzhen University School of Medicine
LanFeng Dong: Griffith University
Bing Yan: Griffith University
Jelena Vider: Griffith University
Stepana Boukalova: Czech Academy of Sciences
Linda Krobova: Czech Academy of Sciences
Katerina Vanova: Czech Academy of Sciences
Renata Zobalova: Czech Academy of Sciences
Margarita Sobol: Czech Academy of Sciences
Pavel Hozak: Czech Academy of Sciences
Silvia Magalhaes Novais: Czech Academy of Sciences
Veronika Caisova: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Pavel Abaffy: Czech Academy of Sciences
Ravindra Naraine: Czech Academy of Sciences
Ying Pang: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Thiri Zaw: Macquarie University
Ping Zhang: Griffith University
Radek Sindelka: Czech Academy of Sciences
Mikael Kubista: Czech Academy of Sciences
Steven Zuryn: Queensland Brain Institute, University of Queensland
Mark P. Molloy: Macquarie University
Michael V. Berridge: Malaghan Institute of Medical Research
Karel Pacak: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health
Jakub Rohlena: Czech Academy of Sciences
Sunghyouk Park: Natural Product Research Institute, Seoul National University
Jiri Neuzil: Griffith University

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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 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.

Date: 2018
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DOI: 10.1038/s41467-018-04603-z

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