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

0492386 - BTÚ 2019 RIV GB eng J - Journal Article
Bezawork-Geleta, A. - Wen, H. - Dong, L. F. - Yan, B. - Vider, J. - Boukalová, Štěpána - Krobová, Linda - Váňová, Kateřina - Zobalová, Renata - Sobol, Margaryta - Hozák, Pavel - Novais, Silvia Magalhaes - Caisova, V. - Abaffy, Pavel - Naraine, Ravindra - Pang, Y. - Zaw, T. - Zhang, P. - Šindelka, Radek - Kubista, Mikael - Zuryn, S. - Molloy, M. P. - Berridge, M.V. - Pacak, K. - Rohlena, Jakub - Park, S. - Neužil, Jiří
Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints.
Nature Communications. Roč. 9, JUN 7 2018 (2018), č. článku 2221. E-ISSN 2041-1723
R&D Projects: GA ČR GA15-02203S; GA MZd NV17-30138A; GA ČR GA17-20904S; GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR GA16-22823S
Institutional support: RVO:86652036 ; RVO:68378050
Keywords : ELECTRON-TRANSPORT CHAIN * PYRUVATE-KINASE M2 * MITOCHONDRIAL-DNA MUTATIONS
OECD category: Biochemistry and molecular biology; Biochemistry and molecular biology (UMG-J)
Impact factor: 11.878, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0286410