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

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 F

SUBMITTER: Miozzo F 

PROVIDER: S-EPMC8931002 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature