RRC ID 83741
Author Zhang F, Lee A, Freitas AV, Herb JT, Wang ZH, Gupta S, Chen Z, Xu H.
Title A transcription network underlies the dual genomic coordination of mitochondrial biogenesis.
Journal Elife
Abstract Mitochondrial biogenesis requires the expression of genes encoded by both the nuclear and mitochondrial genomes. However, aside from a handful transcription factors regulating specific subsets of mitochondrial genes, the overall architecture of the transcriptional control of mitochondrial biogenesis remains to be elucidated. The mechanisms coordinating these two genomes are largely unknown. We performed a targeted RNAi screen in developing eyes with reduced mitochondrial DNA content, anticipating a synergistic disruption of tissue development due to impaired mitochondrial biogenesis and mitochondrial DNA (mtDNA) deficiency. Among 638 transcription factors annotated in the Drosophila genome, 77 were identified as potential regulators of mitochondrial biogenesis. Utilizing published ChIP-seq data of positive hits, we constructed a regulatory network revealing the logic of the transcription regulation of mitochondrial biogenesis. Multiple transcription factors in core layers had extensive connections, collectively governing the expression of nearly all mitochondrial genes, whereas factors sitting on the top layer may respond to cellular cues to modulate mitochondrial biogenesis through the underlying network. CG1603, a core component of the network, was found to be indispensable for the expression of most nuclear mitochondrial genes, including those required for mtDNA maintenance and gene expression, thus coordinating nuclear genome and mtDNA activities in mitochondrial biogenesis. Additional genetic analyses validated YL-1, a transcription factor upstream of CG1603 in the network, as a regulator controlling CG1603 expression and mitochondrial biogenesis.
Volume 13
Published 2024-12-27
DOI 10.7554/eLife.96536
PII 96536
PMID 39727307
PMC PMC11677238
MeSH Animals DNA, Mitochondrial / genetics DNA, Mitochondrial / metabolism Drosophila / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / metabolism Gene Regulatory Networks* Genome, Mitochondrial / genetics Mitochondria / genetics Mitochondria / metabolism Organelle Biogenesis* RNA Interference Transcription Factors* / genetics Transcription Factors* / metabolism Transcription, Genetic
IF 7.08
Resource
Drosophila DGRC#141919