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Citation
Zhou, J., Xu, L., Duan, X., Liu, W., Zhao, X., Wang, X., Shang, W., Fang, X., Yang, H., Jia, L., Bai, J., Zhao, J., Wang, L., Tong, C. (2019). Large-scale RNAi screen identified Dhpr as a regulator of mitochondrial morphology and tissue homeostasis.  Sci. Adv. 5(9): eaax0365.
FlyBase ID
FBrf0243587
Publication Type
Research paper
Abstract

Mitochondria are highly dynamic organelles. Through a large-scale in vivo RNA interference (RNAi) screen that covered around a quarter of the Drosophila melanogaster genes (4000 genes), we identified 578 genes whose knockdown led to aberrant shapes or distributions of mitochondria. The complex analysis revealed that knockdown of the subunits of proteasomes, spliceosomes, and the electron transport chain complexes could severely affect mitochondrial morphology. The loss of Dhpr, a gene encoding an enzyme catalyzing tetrahydrobiopterin regeneration, leads to a reduction in the numbers of tyrosine hydroxylase neurons, shorter lifespan, and gradual loss of muscle integrity and climbing ability. The affected mitochondria in Dhpr mutants are swollen and have fewer cristae, probably due to lower levels of Drp1 S-nitrosylation. Overexpression of Drp1, but not of S-nitrosylation-defective Drp1, rescued Dhpr RNAi-induced mitochondrial defects. We propose that Dhpr regulates mitochondrial morphology and tissue homeostasis by modulating S-nitrosylation of Drp1.

PubMed ID
PubMed Central ID
PMC6750926 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
File date: 2019.10.16 ; File size: 10498 ; File format: tsv ; File name: FBrf0243587.FTYP.2019.10.16.tsv
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Sci. Adv.
    Title
    Science advances
    ISBN/ISSN
    2375-2548
    Data From Reference
    Alleles (147)
    Genes (110)
    Human Disease Models (2)
    Natural transposons (1)
    Experimental Tools (3)
    Transgenic Constructs (144)