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Citation
Yang, C.S., Thomenius, M.J., Gan, E.C., Tang, W., Freel, C.D., Merritt, T.J., Nutt, L.K., Kornbluth, S. (2010). Metabolic regulation of Drosophila apoptosis through inhibitory phosphorylation of Dronc.  EMBO J. 29(18): 3196--3207.
FlyBase ID
FBrf0211843
Publication Type
Research paper
Abstract

Apoptosis ensures tissue homeostasis in response to developmental cues or cellular damage. Recently reported genome-wide RNAi screens have suggested that several metabolic regulators can modulate caspase activation in Drosophila. Here, we establish a previously unrecognized link between metabolism and Drosophila apoptosis by showing that cellular NADPH levels modulate the initiator caspase Dronc through its phosphorylation at S130. Depletion of NADPH removed this inhibitory phosphorylation, resulting in the activation of Dronc and subsequent cell death. Conversely, upregulation of NADPH prevented Dronc-mediated apoptosis upon DIAP1 RNAi or cycloheximide treatment. Furthermore, this CaMKII-mediated phosphorylation of Dronc hindered Dronc activation, but not its catalytic activity. Blockade of NADPH production aggravated the death-inducing activity of Dronc in specific neurons, but not in the photoreceptor cells of the eyes of transgenic flies; similarly, non-phosphorylatable Dronc was more potent than wild type in triggering specific neuronal apoptosis. Our observations reveal a novel regulatory circuitry in Drosophila apoptosis, and, as NADPH levels are elevated in cancer cells, also provide a genetic model to understand aberrations in cancer cell apoptosis resulting from metabolic alterations.

PubMed ID
PubMed Central ID
PMC2944066 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

UAS-Nc lines from FBrf0211843.
Sinenko and Kornbluth, 2014.5.14, UAS-Nc lines from FBrf0211843. [FBrf0225074]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    EMBO J.
    Title
    The EMBO Journal
    Publication Year
    1982-
    ISBN/ISSN
    0261-4189
    Data From Reference
    Alleles (7)
    Genes (9)
    Physical Interactions (2)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (2)
    Transgenic Constructs (6)