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Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans.

Publication ,  Journal Article
Maglioni, S; Schiavi, A; Melcher, M; Brinkmann, V; Luo, Z; Laromaine, A; Raimundo, N; Meyer, JN; Distelmaier, F; Ventura, N
Published in: Nature communications
May 2022

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.

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Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

May 2022

Volume

13

Issue

1

Start / End Page

2620

Related Subject Headings

  • Mitochondrial Diseases
  • Mitochondria
  • Lutein
  • Caenorhabditis elegans Proteins
  • Caenorhabditis elegans
  • Animals
 

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Maglioni, S., Schiavi, A., Melcher, M., Brinkmann, V., Luo, Z., Laromaine, A., … Ventura, N. (2022). Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans. Nature Communications, 13(1), 2620. https://doi.org/10.1038/s41467-022-29972-4
Maglioni, Silvia, Alfonso Schiavi, Marlen Melcher, Vanessa Brinkmann, Zhongrui Luo, Anna Laromaine, Nuno Raimundo, Joel N. Meyer, Felix Distelmaier, and Natascia Ventura. “Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans.Nature Communications 13, no. 1 (May 2022): 2620. https://doi.org/10.1038/s41467-022-29972-4.
Maglioni S, Schiavi A, Melcher M, Brinkmann V, Luo Z, Laromaine A, et al. Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans. Nature communications. 2022 May;13(1):2620.
Maglioni, Silvia, et al. “Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein in C. elegans.Nature Communications, vol. 13, no. 1, May 2022, p. 2620. Epmc, doi:10.1038/s41467-022-29972-4.
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. Nature communications. 2022 May;13(1):2620.

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

May 2022

Volume

13

Issue

1

Start / End Page

2620

Related Subject Headings

  • Mitochondrial Diseases
  • Mitochondria
  • Lutein
  • Caenorhabditis elegans Proteins
  • Caenorhabditis elegans
  • Animals