Abstract
The heat shock (HS) response is essential for survival of all organisms. Although the machinery of the HS response has been extensively investigated at the cellular level, it is poorly understood at the level of the organism. Here, we show the crucial role of the mushroom body (MB) in the HS response in Drosophila. Null mutants of the mitochondrial phosphatase Drosophila PGAM5 (dPGAM5) exhibited increased vulnerability to HS, which was reversed by MB-specific expression of the caspase inhibitor p35, and similar vulnerability was induced in wild-type flies by knockdown of MB dPGAM5. Elimination of the MB did not affect the HS response of wild-type flies, but did increase the resistance of dPGAM5-deficient flies to HS. Thus, the MB may possess an apoptosis-dependent toxic function, the suppression of which by dPGAM5 appears to be crucial for HS resistance.
Highlights
Increases in temperature threaten all living organisms due to heat shock (HS) stress
PGAM51/Y; c739-GAL4/UAS-Histone2B::ECFP (PGAM51) flies showed neither resistance nor sensitivity to oxidative stress (H2O2) and starvation, they were sensitive to HS stress and died sooner than control flies (Fig. 1A), suggesting that Drosophila Phosphoglycerate mutase 5 (PGAM5) (dPGAM5) is required for proper response to HS
Since it was previously found that introduction of the PGAM51 allele into a loss-of-function allele for Drosophila PTEN-induced kinase 1 (PINK1), PINK1B9, ameliorated pathological changes induced by dPINK1 deficiency [11], we examined the genetic interaction between dPGAM5 and dPINK1 in the context of HS response
Summary
Increases in temperature threaten all living organisms due to heat shock (HS) stress. In order to adapt to or resist HS stress, the cellular expression of a series of HS proteins (HSPs) is induced. Cells undergo apoptosis or necrosis when subjected to severe and/or prolonged HS stress that exceeds the capacity of the protective HS response via HSPs [2]. The mechanisms of HS-induced apoptosis have been the focus of intense investigation and are generally well characterized in cultured mammalian cells. At the level of the whole organism, the significance of cellular apoptosis in the HS response has not been as intensively investigated. Model animals such as Caenorhabditis elegans and Drosophila melanogaster are expected to provide useful whole-body assay systems. HS-induced apoptosis has already been clearly demonstrated in the C. elegans germline and the Drosophila wing imaginal disc [5,6]
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