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Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation
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SYSNO ASEP 0523004 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation Author(s) Perez-Gomez, Raquel (BC-A) RID, ORCID
Magnin, Valentina (BC-A)
Mihajlović, Zorana (BC-A)
Slaninová, Věra (BC-A)
Krejčí, Alena (BC-A) RID, ORCIDNumber of authors 5 Article number 4401 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 10, č. 1 (2020)Number of pages 13 s. Language eng - English Country GB - United Kingdom Keywords mitochondria dysfunction ; complex I ; TOR signalling Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GA17-17529S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support BC-A - RVO:60077344 UT WOS 000563372900003 EID SCOPUS 85081607911 DOI 10.1038/s41598-020-61244-3 Annotation Mitochondrial dysfunctions belong amongst the most common metabolic diseases but the signalling networks that lead to the manifestation of a disease phenotype are often not well understood. We identified the subunits of respiratory complex I, III and IV as mediators of major signalling changes during Drosophila wing disc development. Their downregulation in larval wing disc leads to robust stimulation of TOR activity, which in turn orchestrates a complex downstream signalling network. Specifically, after downregulation of the complex I subunit ND-49 (mammalian NDUFS2), TOR activates JNK to induce cell death and ROS production essential for the stimulation of compensatory apoptosis-induced proliferation within the tissue. Additionally, TOR upregulates Notch and JAK/STAT signalling and it directs glycolytic switch of the target tissue. Our results highlight the central role of TOR signalling in mediating the complex response to mitochondrial respiratory dysfunction and they provide a rationale why the disease symptoms associated with respiratory dysfunctions are often alleviated by mTOR inhibitors. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2021 Electronic address https://www.nature.com/articles/s41598-020-61244-3.pdf
Number of the records: 1