Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation

0523004 - BC 2021 RIV GB eng J - Článek v odborném periodiku
Perez-Gomez, Raquel - Magnin, Valentina - Mihajlović, Zorana - Slaninová, Věra - Krejčí, Alena
Downregulation of respiratory complex I mediates major signalling changes triggered by TOR activation.
Scientific Reports. Roč. 10, č. 1 (2020), č. článku 4401. ISSN 2045-2322. E-ISSN 2045-2322
Grant CEP: GA ČR(CZ) GA17-17529S
Institucionální podpora: RVO:60077344
Klíčová slova: mitochondria dysfunction * complex I * TOR signalling
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 4.380, rok: 2020
Způsob publikování: Open access
https://www.nature.com/articles/s41598-020-61244-3.pdf

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.
Trvalý link: http://hdl.handle.net/11104/0315283