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

Miozzo, Federico; Valencia-Alarcón, Eva P; Stickley, Luca; Majcin Dorcikova, Michaëla; Petrelli, Francesco; Tas, Damla; Loncle, Nicolas; Nikonenko, Irina; Bou Dib, Peter; Nagoshi, Emi (2022). Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor. Nature Communications, 13(1), p. 1426. Springer Nature 10.1038/s41467-022-29075-0

Preview

Text s41467-022-29075-0.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (7MB) | Preview

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 Fer2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modeling and treating PD.

Interest & Impact

Downloads

49 since deposited on 21 Mar 2022
35 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item