| Citation | Maglioni S, Schiavi A, Melcher M, Brinkmann V, Luo Z, Laromaine A, Raimundo N, Meyer JN, Distelmaier F, Ventura N. Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans. Nat Commun, 2022. |
| PubMed ID | 35551180 |
| Short Description | Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans. GEO Record: GSE144573 GSE144574 Platform: GPL19230 Download gene-centric, log2 transformed data: WBPaper00064182.ce.mr.csv |
| # of Conditions | 12 |
Full Description
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Complex-I-deficiency represents the most frequent pathogenetic cause of human mitochondriopathies. Therapeutic options for these neurodevelopmental life-threating disorders do not exist, partly due to the scarcity of appropriate model systems to study them. Caenorhabditis elegans is a genetically tractable model organism widely used to investigate neuronal pathologies. Here, we generate C. elegans models for mitochondriopathies and show that depletion of complex I subunits recapitulates biochemical, cellular and neurodevelopmental aspects of the human diseases. We exploit two models, nuo-5/NDUFS1- and lpd-5/NDUFS4-depleted animals, for a suppressor screening that identifies lutein for its ability to rescue animals' neurodevelopmental deficits. We uncover overexpression of synaptic neuroligin as an evolutionarily conserved consequence of mitochondrial dysfunction, which we find to mediate an early cholinergic defect in C. elegans. We show lutein exerts its beneficial effects by restoring neuroligin expression independently from its antioxidant activity, thus pointing to a possible novel pathogenetic target for the human disease. Experimental Details: WBPaper00064182:N2_repI WBPaper00064182:N2_repIII WBPaper00064182:N2_repIV WBPaper00064182:N2_repV WBPaper00064182:nuo-5(RNAi)-mild_repI WBPaper00064182:nuo-5(RNAi)-mild_repIII WBPaper00064182:nuo-5(RNAi)-mild_repIV WBPaper00064182:nuo-5(RNAi)-mild_repV WBPaper00064182:nuo-5(RNAi)-strong_repI WBPaper00064182:nuo-5(RNAi)-strong_repIII WBPaper00064182:nuo-5(RNAi)-strong_repIV WBPaper00064182:nuo-5(RNAi)-strong_repV. |
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