PT - JOURNAL ARTICLE AU - David Cruz-Garcia AU - Nathalie Brouwers AU - Vivek Malhotra AU - Amy J. Curwin TI - Reactive oxygen species (ROS) production triggers unconventional secretion of antioxidant enzymes AID - 10.1101/628321 DP - 2019 Jan 01 TA - bioRxiv PG - 628321 4099 - http://biorxiv.org/content/early/2019/05/05/628321.short 4100 - http://biorxiv.org/content/early/2019/05/05/628321.full AB - Nutrient deprivation triggers the release of signal-sequence-lacking antioxidant superoxide dismutase 1 (SOD1). We now report that secreted SOD1 is functionally active and accompanied by export of other antioxidant enzymes such as thioredoxins, (Trx1 and Trx2) and peroxiredoxin Ahp1. Our data reveal that starvation increases mitochondrial activity, which generates higher, but non-toxic, levels of reactive oxygen species (ROS). Inhibiting mitochondrial activity or ROS prevents antioxidants secretion. We suggest that in response to ROS production that can permeate the plasma membrane, the cells respond by secreting antioxidants to prevent ROS-mediated damage in the extracellular space. These findings provide an understanding of why cells secrete signal sequence lacking antioxidant enzymes in response to starvation.