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 KubistaSteven Zuryn, Mark P. Molloy, Michael V. Berridge, Karel Pacak, Jakub Rohlena, Sunghyouk Park, Jiri Neuzil

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)
38 Downloads (Pure)

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.

Original languageEnglish
Article number2221
Pages (from-to)1-17
Number of pages17
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 7 Jun 2018

Bibliographical note

Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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