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.
- MeSH
- down regulace MeSH
- Drosophila MeSH
- Janus kinasy metabolismus MeSH
- křídla zvířecí růst a vývoj metabolismus MeSH
- proteiny Drosophily genetika metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- receptory Notch metabolismus MeSH
- respirační komplex I genetika metabolismus MeSH
- signální transdukce * MeSH
- transkripční faktory STAT metabolismus MeSH
- tyrosinkinasové receptory metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
