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Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints
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SYSNO ASEP 0492386 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints Author(s) Bezawork-Geleta, A. (AU)
Wen, H. (CN)
Dong, L. F. (AU)
Yan, B. (AU)
Vider, J. (AU)
Boukalová, Štěpána (BTO-N)
Krobová, Linda (BTO-N)
Váňová, Kateřina (BTO-N)
Zobalová, Renata (BTO-N) RID
Sobol, Margaryta (UMG-J) RID
Hozák, Pavel (UMG-J) RID, ORCID
Novais, Silvia Magalhaes (BTO-N)
Caisova, V. (US)
Abaffy, Pavel (BTO-N)
Naraine, Ravindra (BTO-N)
Pang, Y. (US)
Zaw, T. (AU)
Zhang, P. (AU)
Šindelka, Radek (BTO-N) RID
Kubista, Mikael (BTO-N) RID
Zuryn, S. (AU)
Molloy, M. P. (AU)
Berridge, M.V. (NZ)
Pacak, K. (US)
Rohlena, Jakub (BTO-N) RID, ORCID
Park, S. (KR)
Neužil, Jiří (BTO-N) RIDNumber of authors 27 Article number 2221 Source Title Nature Communications. - : Nature Publishing Group
Roč. 9, JUN 7 2018 (2018)Number of pages 17 s. Language eng - English Country GB - United Kingdom Keywords ELECTRON-TRANSPORT CHAIN ; PYRUVATE-KINASE M2 ; MITOCHONDRIAL-DNA MUTATIONS Subject RIV EB - Genetics ; Molecular Biology OECD category Biochemistry and molecular biology Subject RIV - cooperation Institute of Molecular Genetics R&D Projects GA15-02203S GA ČR - Czech Science Foundation (CSF) NV17-30138A GA MZd - Ministry of Health (MZ) GA17-20904S GA ČR - Czech Science Foundation (CSF) LM2015062 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA16-22823S GA ČR - Czech Science Foundation (CSF) Institutional support BTO-N - RVO:86652036 ; UMG-J - RVO:68378050 UT WOS 000434379800018 EID SCOPUS 85048232435 DOI 10.1038/s41467-018-04603-z Annotation 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2019
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