Redox regulation of LSD1/CATALASE 2 phase separation condensates controls location and functions

Phase separation of proteins is emerging as an important mechanism of oxidative stress regulation and protein trafficking. We show Arabidopsis catalase 2 (CAT2), is recruited to phase-separated condensates with LESION STIMULATING DISEASE1 (LSD1), a plant specific regulator of programmed cell death, in a redox-dependent manner that regulates its intracellular localisation and activity. The ability of LSD1 to form phase-separated condensates is a property of Zinc Fingers 1 and 2. CAT2 and LSD1 form ternary complexes with the peroxisome import receptor PEX5, and the distribution of all three proteins and the fluidity of the LSD1 condensates is regulated by redox state. In vivo trafficking of CAT2 to peroxisomes and the nuclei is redox regulated, and LSD1 controls CAT2 localisation in vivo . We propose a model whereby the redox-dependent differential accessibility of CAT2, PEX5 and LSD1 within condensates not only regulates CAT2 activity but also trafficking between peroxisome, cytosol and nucleus.