The photolyase/cryptochrome of Aspergillus nidulans senses oxidative stress and shuttles from nuclei to mitochondria

Cryptochromes are photoreceptors with functions in the entrainment of circadian clocks or as proposed magnetoreceptors in birds or as lightindependent regulators of stress responses in plants. Here, we show that the fungal cryptochrome-like photolyase CryA from Aspergillus nidulans is induced by light and oxidative stress and establishes negative-feedback loops for lightand stress-activated genes. The negative-feedback loops depend on CryA interaction with phytochrome and the HOG (high osmolarity glycerol) pathway transcription factor AtfA in nuclei. CryA translocated in less than one minute from nuclei to mitochondria in the presence of hydrogen peroxide suggesting mitochondrial functions and possibly mitochondrialnuclear communication. The shuttle to mitochondria depended on the N-terminal extension and a cysteine therein, which probably induces conformational changes of CryA upon oxidation. Therefore, we propose CryA as a sensor for oxidative stress. Such an N-terminal extension is also present in other photolyases and some cryptochromes, suggesting evolutionary conservation of the mechanism.