LAUSR

The Lon protease plays a key role in mitochondrial proteostasis. We find that young female D. melanogaster flies, but not males, adapt to very low and non-damaging (micromolar), signaling, levels of H2O2 through the CncC (Nrf2 orthologue) signal transduction pathway. In contrast, young male flies adapt to redox cycling agents paraquat and menadione, whereas females do not. This is an example of physiological Adaptive Homeostasis as recently defined (Davies, K.J.A. Adaptive Homeostasis, Molecular Aspects of Medicine 49, 1–7, 2016) rather than a response to toxicity or a damage-repair phenomenon. Adaptation in both females and males is observed in young (3 day) flies, but this inducibility is lost with age (60 day flies). When Lon induction is blocked with a ‘gene-switch’ expressing Lon RNAi, adaptation is attenuated. To assess Lon’s involvement in the male and female adaptive differences, males were transformed into ‘pseudo-females’ through over-expression of the female-specific Transformer (TraF) splicing factor. Pseudo-females recapitulated the female-specific H2O2 adaptation phenotype. Similarly, when females were transformed into pseudo-males, they recapitulated the male-specific paraquat/menadione adaptation phenotype. Clearly, mitochondrial metabolism is important in both sex- and age- specific adaptation and redox signaling pathways.