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Citation
Fukuoh, A., Cannino, G., Gerards, M., Buckley, S., Kazancioglu, S., Scialo, F., Lihavainen, E., Ribeiro, A., Dufour, E., Jacobs, H.T. (2014). Screen for mitochondrial DNA copy number maintenance genes reveals essential role for ATP synthase.  Mol. Syst. Biol. 10(6): 734.
FlyBase ID
FBrf0225413
Publication Type
Research paper
Abstract
The machinery of mitochondrial DNA (mtDNA) maintenance is only partially characterized and is of wide interest due to its involvement in disease. To identify novel components of this machinery, plus other cellular pathways required for mtDNA viability, we implemented a genome-wide RNAi screen in Drosophila S2 cells, assaying for loss of fluorescence of mtDNA nucleoids stained with the DNA-intercalating agent PicoGreen. In addition to previously characterized components of the mtDNA replication and transcription machineries, positives included many proteins of the cytosolic proteasome and ribosome (but not the mitoribosome), three proteins involved in vesicle transport, some other factors involved in mitochondrial biogenesis or nuclear gene expression, > 30 mainly uncharacterized proteins and most subunits of ATP synthase (but no other OXPHOS complex). ATP synthase knockdown precipitated a burst of mitochondrial ROS production, followed by copy number depletion involving increased mitochondrial turnover, not dependent on the canonical autophagy machinery. Our findings will inform future studies of the apparatus and regulation of mtDNA maintenance, and the role of mitochondrial bioenergetics and signaling in modulating mtDNA copy number.
PubMed ID
PubMed Central ID
PMC4265055 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Syst. Biol.
    Title
    Molecular Systems Biology
    Publication Year
    2005-
    ISBN/ISSN
    1744-4292
    Data From Reference