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Scientific article
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Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor

Published inNature communications, vol. 13, p. 1-18; 1426
Publication date2022-03-17
First online date2022-03-17
Abstract

Progressive degeneration of dopaminergic (DA) neurons in the substantia nigra is a hallmark of Parkinson’s disease (PD). Dysregulation of developmental transcription factors is implicated in dopaminergic neurodegeneration, but the underlying molecular mechanisms remain largely unknown. Drosophila Fer2 is a prime example of a developmental transcription factor required for the birth and maintenance of midbrain DA neurons. Using an approach combining ChIP-seq, RNA-seq, and genetic epistasis experiments with PD-linked genes, here we demonstrate that Fer2 controls a transcriptional network to maintain mitochondrial structure and function, and thus confers dopaminergic neuroprotection against genetic and oxidative insults. We further show that conditional ablation of Nato3 , a mouse homolog of Fer2 , in differentiated DA neurons causes mitochondrial abnormalities and locomotor impairments in aged mice. Our results reveal the essential and conserved role of Fer 2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modeling and treating PD.

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Citation (ISO format)
MIOZZO, Federico et al. Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor. In: Nature communications, 2022, vol. 13, p. 1–18. doi: 10.1038/s41467-022-29075-0
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ISSN of the journal2041-1723
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